Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SPLEEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

Noradrenergic and peptidergic innervation of the amphibian spleen: comparative studies.

Spleens from representatives of the three amphibian orders were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence to detect catecholamines and immunocytochemistry to detect several neural antigens. Nerve fibers are scattered throughout the spleens of adult salamanders (Taricha torosa, Notophthalmus viridescens, and Ambystoma mexicanum). A less abundant but similarly diffuse pattern of innervation characterizes the spleen of the caecilian, Typhlonectes sp. The spleen of the adult frog, Xenopus laevis, is separated into clearly defined compartments of red pulp and white pulp, much as is seen in the mammalian spleen. As in mammals, sympathetic innervation of the Xenopus spleen is noradrenergic (NA) and confined to the white pulp. The white pulp of Xenopus spleen also contains fibers which stain for neuropeptide Y and substance P. The spleen of the anuran, Rana pipiens, is also highly compartmentalized, with tyrosine hydroxylase positive fibers in proximity to blood vessels. These findings provide an anatomical substrate for neural-immune interactions in the Amphibia.

Amphibians↗
PubMed1998

Oral administration of one dose of cholera toxin induces a systemic immune response prior to a mucosal immune response by a direct presentation in the spleen.

In the present report the results indicate that the oral administration of one dose of CT in rats results in an antibody immune response in the spleen 48 h later, whereas no antitoxin antibody forming cells were found in the Peyer patches (PP), mesenteric lymph node (MLN) and lamina propria (LP) of the small intestine. At this time the main isotype of the antitoxin antibodies in the spleen were IgG and IgM, 5 days after the priming, few antitoxin AFC were observed in the MLN, IgG being the main isotype, whereas no IgM antitoxin AFC were found. At 1 week after priming the number of antitoxin AFC in the MLN reached similar values to those observed in the spleen. When cells from the spleen of rats primed orally with one dose of CT were cultured during 4 days in the presence of inhibitory doses of anti-Ia MAb (OX6), the number of antitoxin AFC was diminished when compared with that observed when cells were cultured in the absence of anti-Ia. The main isotype of antitoxin AFC observed when cells were analyzed after culture was IgM and it was the isotype most affected by the treatment with MAb anti-Ia. These results strongly suggest that an in situ presentation of the antigen did occur in the spleen. On the other hand, when the secondary immune response was studied 48 h after boosting, antitoxin AFC were found in the PP, MLN, SP and LP and 5 days after the booster a 20-30-fold increase was observed in all lymphoid tissues studied, indicating that the secondary immune response found in the spleen was mainly due to the recruitment of memory cells from Peyer's patches. However, when spleen cells were cultured 48 h after the immunization in the presence of inhibitory doses of anti-Ia a little decrease in the number of AFC was observed when compared with the controls (in absence of anti-Ia). The analysis of the antitoxin antibodies in sera and intestinal fluids were in line with the results presented above. The results shown in this report indicate that the systemic immune response observed after the oral administration of CT could be due in part to an in situ presentation of the antigen in the systemic compartments, especially in the spleen.

Administration, Oral↗
PubMed1998

Restoration of sympathetic noradrenergic nerve fibers in the spleen by low doses of L-deprenyl treatment in young sympathectomized and old Fischer 344 rats.

It is well-established that noradrenergic (NA) nerve fibers in spleen and lymph nodes influence cell-mediated immune responses. Such responses are diminished in young animals following chemical sympathectomy and in older animals accompanying an age-related decline in NA nerve fibers in spleen and lymph nodes. The purpose of this study was to determine whether treatment with deprenyl, an irreversible monoamine oxidase-B (MAO-B) inhibitor, would hasten the process of splenic NA reinnervation following chemical sympathectomy in young rats and would reverse the age-related loss of sympathetic NA fibers in the spleen of old rats. To examine the effects of deprenyl in young sympathectomized rats, 3-month-old male Fischer 344 (F344) rats were treated with 6-hydroxydopamine (6-OHDA) and administered 0, 0.25, 1.0, 2.5, or 5.0 mg deprenyl/kg body weight (BW)/day intraperitoneally (i.p.) for 1, 15, or 30 days. In another study, 21-month-old male F344 rats were treated with 0, 0.25, or 1.0 mg deprenyl/kg BW/day i.p. for 9 weeks. At the end of the treatment period, spleens were removed and NA innervation was assessed by fluorescence histochemistry, immunocytochemistry, and quantitation of norepinephrine (NE) by high performance liquid chromatography with electrochemical detection (HPLC-EC). In the spleens of young sympathectomized rats, there was faint fluorescence or absence of fluorescence and tyrosine hydroxylase-positive (TH+) fibers around the central arteriole and in the periarteriolar lymphatic sheath of the white pulp one day after administration of 6-OHDA, indicating a severe loss of NA innervation compared with unlesioned control animals. Treatment of sympathectomized rats with 1.0 mg, 2.5 mg, and 5.0 mg/kg deprenyl for 30 days increased the density of NA innervation estimated by both fluorescence histochemistry and immunocytochemistry compared with vehicle-treated controls recovering spontaneously from 6-OHDA. Splenic NE concentration was increased in the hilar region of sympathectomized rats treated with 2.5 mg and 1.0 mg/kg deprenyl after 15 and 30 days, respectively, compared with untreated and vehicle-treated sympathectomized rats. The spleens of untreated and saline-treated old rats showed a reduction in the density of NA innervation in the white pulp compared with young animals. Treatment of old rats for 9 weeks with 1.0 mg/kg deprenyl induced moderate to intense fluorescent fibers and linear TH+ nerve fibers around the central arteriole and in other compartments of the white pulp, and increased splenic NE concentration in the hilar region and NE content in the whole spleen. Taken together, these results provide strong evidence for a neurorestorative property of deprenyl on sympathetic NA innervation of the spleen, which may lead to an improvement in cell-mediated immune responses.

Adrenergic Fibers↗
PubMed1980

Studies of the producer cell of herpes simplex virus-induced interferon in mouse spleen cell cultures.

The producer cell of type I interferon was studied in spleen cell cultures of C57BL/6 mice stimulated by inactivated Herpes Simplex Virus (HSV). Interferon production was not abolished by pretreatment of the spleen cells by anti-theta serum plus complement. The producer cell of interferon was not removed by plastic adherence and was not destroyed by the addition of silica. It was present in spleens of 3 day old C57BL/6 mice and in spleens of nu/nu mice. It was not inactivated by treatment of nu/nu spleen cells by anti-theta serum plus complement. HSV-induced interferon production was abolished by passage of the spleen cells through nylon wool columns and by irradiation (1000 R) of the spleen cells. Collectively these data suggest that in murine spleen cell cultures type I interferon is produced by B cells. However, our data do not allow to rule out that the interferon producing cell may be an immature macrophage or an immature T cell.

Animals↗
PubMed2003

Immunomodulatory effects of aqueous-extracted Astragali radix in methotrexate-treated mouse spleen cells.

The present study was conducted to evaluate the immunomodulatory effect of aqueous-extracted Astragali radix (ARE) in methotrexate (MTX)-treated mouse spleen cells. In spleen cell proliferation assay, ARE enhanced mitogenic activity in the dose-response manner. We also investigated the effect of ARE on the reducing of immune suppression caused by MTX in mouse spleen cells. MTX decreased the spleen cell proliferation (IC(50):800 microg/ml). However, ARE significantly reduced the suppression of cell proliferation by MTX in mouse spleen cells. Immunomodulatory effect of ARE were further investigated using reverse transcription polymerase chain reaction (RT-PCR). In RT-PCR, we examined the expressions of various cytokines such as IL-6, IL-1alpha, IL-1beta, IL-12p40, GM-CSF and TNF. Enhancement of IL-1alpha and IL-12p40 mRNA expressions were shown in mouse spleen cells by ARE. In spite of MTX treatment, the expressions of IL-1alpha and IL-12p40 mRNA sustained in spleen cells. These data indicate that (1) ARE has a protective effect of immune suppression, and (2) the immunomodulatory effects of ARE may be, in part, associated with the expressions of IL-1alpha and IL-12p40 mRNA as well as the mitogenic effect on spleen cells.

Adjuvants, Immunologic↗
PubMedDate not supplied

Large quantity of ribosomal RNA exists extracellularly in mouse spleen.

When BALB/c mouse spleens were gently homogenized in saline, the resultant supernatant (without cells and tissue debris) contained significant amount of 28S and 18S ribosomal RNA, reaching up to 70% of the total spleen RNA. Haemoglobin assays indicated that less than 15% of the spleen cells were lysed during the homogenization process, indicating that the majority of the spleen 'supernatant RNA' was from the extracellular space of the organ rather than released by the splenocytes as a consequence of grinding. Quantitative RNA analysis showed that the ratio of spleen supernatant RNA/total RNA of BALB/c mice was inversely correlated with age (from approximately 70% at 3 weeks to 45% at 6 months), but that of BXSB mice (an animal model for systemic lupus erythematosus) remained at about 70% irrespective of age. Methyl Green-Pyronin Y staining of paraffin sections of mouse spleen revealed that extracellular RNA was distributed mainly in the sinuses of the organ. Culture supernatants of apoptotic splenocytes contained significant amounts of RNA, suggesting that the extracellular RNA in the spleen might have come from apoptotic lymphocytes. This is supported by the fact that 'thymus supernatant' also contained significant amount of RNA. A possible correlation between spleen extracellular RNA and autoimmune diseases is discussed.

Age Factors↗
PubMedDate not supplied

An antigenic difference between cells forming early and late haematopoietic spleen colonies (CFU-S).

Murine pluripotent haematopoietic stem cells have generally been assayed by their ability to form macroscopic colonies of haematopoietic cells in the spleens of heavily irradiated recipient mice (colony-forming unit-spleen or CFU-S assay). However, recent evidence suggests that there are distinct subpopulations of CFU-S. Most spleen colonies present 7-8 days after injection consist of differentiated erythroid cells, contain no primitive myeloid or erythroid precursor cells and disappear from the spleen within 3 days, whereas the majority of colonies present at 10-12 days contain primitive precursors, are multilineal and cannot be detected at 7-8 days. Furthermore, many 10-day-old spleen colonies do not contain cells capable of forming spleen colonies in secondary irradiated recipients (an index of the self-renewal capacity of stem cells) whereas at day 14 almost all colonies contain these CFU-S. These studies suggest that only when colonies are scored at or later than 11-12 days is the spleen colony technique adequate for the assay of multipotential stem cells. We now report an antigenic difference between subpopulations of CFU-S forming early (day 8) and late (day 14) spleen colonies which has been used to purify multipotential haematopoietic stem cells from murine bone marrow.

Age Factors↗
PubMed1999

Cytolytic activity of mitogen activated old and young mouse spleen cells against tumor target cells expressing high or low levels of Fas antigen.

Sensitivity of Fas expressing tumor cells (high levels in Hut78 & Jurkat; low levels in P815) toward the cytotoxic Con-A (5 microg/ml) activated spleen cells from young (12 to 16 week old males) and old (2 year old males) mice were studied. The spleen cells from young mice activated for a day showed high levels of cytotoxic activity against Hut78 and Jurkat cell lines but not against P815 cells. The cytotoxic activity against P815 cells were detected in the spleen cells from old but not young mice following a longer period of Con-A activation (three days). Comparable levels of cytotoxic activity against Hut78 and Jurkat cells were observed in the spleen cells from both young and old mice following three days of activation. Treatment of Hut78 cells with anti-Fas antibody affected the tumor cells become resistant against the cytotoxic activity of the spleen cells from young mice in a dose dependent manner however P815 cells were not affect by the anti-Fas antibody treatment. These results show that there are differences in the sensitivity of target tumor cells toward Con-A induced cytotoxic spleen cells from young and old mouse. Mitogen-induced cytotoxic lymphocytes from young mouse spleen appear to kill targets through mechanisms involving Fas antigen, specially, in early stage (1 day) of activation. Old mouse spleen cells generated high levels of cytotoxic cells in later phase (3 days), which appear to kill through Fas-unrelated mechanisms.

Age Factors↗
PubMed1990

Comparative study on glucocerebrosidase in spleens from patients with Gaucher disease.

In Gaucher disease (glucosylceramide lipidosis), deficiency of glucocerebrosidase causes pathological storage of glucosylceramide, particularly in the spleen. A comparative biochemical and immunological analysis has therefore been made of glucocerebrosidase in spleens from normal subjects (n = 4) and from Gaucher disease patients with non-neuronopathic (n = 5) and neuronopathic (n = 5) phenotypes. The spleens from all Gaucher disease patients showed markedly decreased glucocerebrosidase activity. Discrimination of different phenotypes of Gaucher disease was not possible on the basis of the level of residual enzyme activity, or by measurements, using the immunopurified enzyme, of kinetic constants, pI or molecular mass forms. A severe decrease was found in the specific activity of glucocerebrosidase purified to homogeneity from the spleen of a patient with the non-neuronopathic phenotype of Gaucher disease, as compared with that of the enzyme purified from the spleen of a normal subject. This finding was confirmed by an immunological method developed for accurate assessment of the relative enzyme activity per molecule of glucocerebrosidase protein. The method revealed that the residual enzyme in the spleens of all investigated patients with a non-neuronopathic course of Gaucher disease had a more than 7-fold decreased activity of glucocerebrosidase (measured in the presence of taurocholate) per molecule of enzyme, and that the concentration of glucocerebrosidase molecules in the spleens of these patients was near normal. Observations made with immunoblotting experiments were consistent with these findings. In contrast, in the spleens of patients with neuronopathic phenotypes of Gaucher disease, the concentration of glucocerebrosidase molecules was severely decreased.

Blood Platelets↗
PubMed1996

Completely allogeneic spleen cells induced cytolytic neonatal tolerance to alloantigens, but failed to establish allo-helper interactions with host T cells.

The injection of spleen cells from F1 mice into-newborns from a parental strain results in the establishment of cytolytic tolerance to donor alloantigens and the development of a lupus-like disease. This syndrome is the consequence of the recognition by alloreactive host CD4+ T cells of discordant major histocompatibility complex (MHC) class II antigens on semi-allogeneic donor B cells. We have analysed whether completely allogeneic spleen cells are as able as semi-allogeneic spleen cells to induce cytolytic tolerance to donor alloantigens and to co-operate with alloreactive T cells for autoantibody production. BALB/c mice were injected at birth with Thy-1-depleted spleen cells from (C57BL/6 x BALB/c)F1 or C57BL/6 mice, either alone or in combination. Cytolytic tolerance was always induced, as manifested by persistence of chimerism and acceptance of skin allografts. However, only F1 semi-allogeneic B cells were activated by alloreactive host T cells to produce anti-DNA IgG antibody. The deficient co-operation between BALB/c CD4+ T cells and completely allogeneic C57BL/6 B cells was confirmed after neonatal injection of (C57BL/ 6 x BALB/c)F1(Igha) spleen cells together with C57BL/6(Ighb) spleen cells. These mice developed anti-DNA antibodies bearing only the Igha allotype. Similar results were observed in experiments of allogeneic interaction in vitro, in which BALB/c CD4+ T cells were cocultured with either (C57BL/6 x BALB/c)F1 or C57BL/6 B cells. The present results demonstrate that completely allogeneic spleen cells efficiently induced cytolytic unresponsiveness to donor alloantigens, but B cells contained in this spleen cell population were unable to establish allo-helper interactions with alloreactive CD4+ T cells, suggesting that cytolytic and helper T-cell interactions involved in alloreactivity may be different.

Animals↗
PubMed2002

The study of T-cell activation in peripheral blood and spleen of hepatosplenic patients suggests an exchange of cells between these two compartments in advanced human Schistosomiasis mansoni infection.

A histopathological and immunophenotypic study was performed on the spleen of patients with hepatosplenic (HS) schistosomiasis mansoni. Morphological data demonstrated that all HS patients presented features related to Schistosoma mansoni-induced splenomegaly, such as red pulp congestion and atrophy/hyperplasia of white pulp. The morphological diversity of the white pulp seems to be associated with the expansion of activated CD4+ T-cell subpopulation. The data obtained suggest that the spleen is an important site for T-cell activation during severe chronic infection with S. mansoni. In addition, we have compared the cell populations/subpopulations presented in the peripheral blood with that observed in the spleen of patients with HS schistosomiasis mansoni. We observed a significant increase in the percentage of activated CD4+HLA-DR+ and CD8+HLA-DR+ T cells in both the spleen and the peripheral blood of HS patients in comparison with noninfected individuals (NOR). These data suggest an exchange of cells between these two compartments. However, we observed normal expression of the CD28 molecule by CD8+ T cells in the spleen, despite a lower percentage of these cells in the peripheral blood. This finding supports the hypothesis that the decrease in CD28 expression, by CD8+ cells, is an event that takes place outside the spleen during human schistosomiasis infection. The most important conclusion is the fact that the analysis of T-cell activation in the peripheral blood reflects the major immunological reactivity that occurs in the spleen during human schistosomiasis and that the morphological aspects of the spleen may reflect the functional activity of T cells. The specificities of T cells and the roles they may play in the pathogenesis during chronic schistosomiasis now need to be determined.

Adolescent↗
PubMed2003

Osteogenic potential of rat spleen stromal cells.

Evidence is mounting that an increasing number of cell populations in the adult organism already committed and/or differentiated retain the ability to reprogram themselves and give rise to a different phenotype. Bone marrow stromal cells have long been recognized as early progenitor cells for osteoblasts, chondrocytes, hematopoietic-supportive fibroblasts and adipocytes. Recent reports though have demonstrated a potential of cell populations outside the bone marrow environment to sustain bone formation under specific circumstances. The formation of bone nodules in the spleen of IL-5 transgenic mice has been recently reported (Macias et al. (2001): J. Clin. Invest. 107, 949 - 959). We thus postulated that a cell population exists in the spleen that under particular microenvironmental conditions is able to reprogram itself and pursue a fate other than the tissue-specific one. Therefore we isolated and expanded in vitro spleen-derived stromal cells. After expansion, these cells were challenged with culture conditions designed to induce osteogenic differentiation. We hypothesized that the combination of a proliferating factor (fibroblast growth factor 2) and a differentiating hormone (dexamethasone) would allow us to induce spleen-derived stromal cells to proliferate and at the same time to express osteoblast-specific genes. Thus, spleen-derived stromal cells were isolated from rat spleen and expanded in the presence of fibroblast growth factor 2 and dexamethasone. Once primary cultures reached confluence they were either switched to an osteo-inductive medium or implanted in immunodeficient mice. Although no bone formation was observed in in vivo experiments, in vitro spleen-derived stromal cells were able to deposit a mineralized matrix. Gene expression, as revealed by RT-PCR analysis, evidenced that the deposition of a mineralized matrix was concomitant with the expression of CBFA1 and osteocalcin, along with alkaline phosphatase and bone sialoprotein. Our data suggest that rat spleen-derived stromal cells can undergo osteogenic differentiation in a permissive microenvironment.

Alkaline Phosphatase↗
PubMed2004

Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor.

UNLABELLED: We examined the effect of PGE2 on OC formation from spleen cells treated with M-CSF and RANKL. PGE2 decreased OC number at 5-6 days of culture and increased OC number, size, and resorptive activity at 7-8 days. A selective EP2 receptor agonist mimicked these effects. Deletion of the EP2 receptor or depletion of T-cells abrogated the increase in OC number. INTRODUCTION: Prostaglandin E2 (PGE2) has been reported to increase osteoclast (OC) number in spleen cells cultured with RANKL and macrophage-colony-stimulating factor (M-CSF). In this study, we examined the time course of PGE2 effects on spleen cells cultured with RANKL and M-CSF. We then investigated which PGE receptors and cell types were involved in these effects. MATERIALS AND METHODS: Spleen cells were cultured from wildtype C57BL/6 mice and EP2 or EP4 receptor-deficient (-/-) and wildtype (+/+) mice on a mixed genetic background. Spleen cells were cultured with M-CSF and RANKL for 5-9 days with or without PGE2 or selective agonists for the four PGE2 receptors (EP1A, EP2A, EP3A, or EP4A). Some cultures were performed using T-cell-depleted spleen cells. OC number and size were quantitated. OC apoptosis and pit formation were measured at 7 or 8 days. RESULTS: PGE2 decreased the number of OCs formed in the presence of RANKL and M-CSF at 5-6 days of culture and increased OC number at 8-9 days compared with cultures without PGE2. PGE2 also increased OC size at 7 and 8 days, decreased apoptosis of OC at 7 days, and increased pit formation at 8 days. EP1A or EP4A had no effect on OC. EP3A decreased OC number. EP2A mimicked effect of PGE2. EP2(-/-) spleen cells showed no increase in OC number in response to PGE2, whereas deletion of EP4 had no effect. Depletion of T-cells abrogated the late increase of OC number. CONCLUSIONS: We conclude that PGE2 has an initial inhibitory effect on OC formation in spleen cell cultures, possibly mediated by both EP2 and EP3 receptors, and a later stimulatory effect, mediated by the EP2 receptor, possibly acting on T-cells.

Animals↗
PubMed2003

Malondialdehyde-protein adducts in the spleens of aniline-treated rats: immunochemical detection and localization.

Previously it was reported that aniline exposure in rats induces increased lipid peroxidation and formation of malondialdehyde (MDA)-protein adducts in the spleen. In order to further elucidate the role of MDA-protein adducts in the splenic toxicity of aniline, studies were conducted to detect and localize these adducts in the spleen. Rabbit polyclonal antisera to MDA-keyhole limpet hemocyanin were employed for immunohistochemical localization and Western blot analyses of MDA-protein adducts in the spleens of aniline-treated (65 mg/kg/d aniline in the drinking water for 30 d) and control rats. For immunohistochemical localization of MDA-protein adducts in the spleen, a new approach using alkaline phosphatase-fast red (red color) to demonstrate bound primary antibodies was adopted, providing a sharper and increased contrast compared to horseradish peroxidase-diaminobenzidine (brown color) methodology. This new approach allowed us to differentiate the changes in aniline-treated spleens, which had extensive brownish deposits of iron proteins. Spleens from aniline-treated rats showed intense staining for these adducts in the red pulp areas (where iron was also localized), especially within the sinusoidal macrophages. Spleens from control rats showed only mild staining for adducts and only traces of iron. Western blot analyses of splenic microsomal proteins from aniline-treated and control rats showed the presence of 13 different MDA-modified proteins. However, 26-, 32-, and 14-kD proteins were more prominent in the aniline-treated rats. The colocalization of MDA-protein adducts with iron in the red pulp of the spleen suggests that iron-catalyzed lipid peroxidation leading to formation of MDA-protein adducts could be a potential mechanism for splenic toxicity of aniline.

Aniline Compounds↗
PubMed1978

Suppressor T-cell activity in responder X nonresponder (C57BL/10 X DBA/1)F1 spleen cells responsive to L-glutamic acid60-L-alanine30-L-tyrosine10.

The ability of spleen cells from (responder X nonresponder)F(1) mice immunized with various GAT-Mphi, GAT-MBSA, and soluble GAT to develop IgG GAT-specific PFC responses in vitro after stimulation with responder and nonresponder parental and F(1) GAT-Mphi, was investigated. F(1) spleen cells from mice immunized with F(1) GAT-Mphi or GAT-MBSA developed secondary responses to responder and nonresponder parental and F(1) GAT- Mphi, but not to unrelated third party GAT-Mphi. Spleen cells from F(1) mice immunized with either parental GAT-Mphi developed secondary responses to F(1) GAT-Mphi and only the parental GAT-Mphi used for immunization in vivo. Soluble GAT-primed F(1) spleen cells responded to F(1) and responder parental, but not nonresponder parental, GAT-Mphi. Simultaneous immunization in vivo with the various GAT-Mphi or GAT-MBSA plus soluble GAT modulated the response pattern of these F(1) spleen cells such that they developed secondary responses only to F(1) and parental responder GAT-Mphi regardless of the response pattern observed after immunization with the various GAT-Mphi or GAT-MBSA alone. These observations demonstrate the critical importance of the physical state of the GAT used for immunization in determining the subsequent response pattern of immune F(1) spleen cells to the parental and F(1) GAT-Mphi. Further, suppressor T cells, capable of inhibiting primary responses to GAT by virgin F(1) spleen cells stimulated by nonresponder parental GAT-Mphi, were demonstrated in spleens of F(1) mice immunized with soluble GAT, but not those primed with F(1) GAT-Mphi. Because responder parental mice develop both helper and suppressor T cells after immunization with GAT-Mphi, and soluble GAT preferentially stimulates suppressor T cells whereas GAT-Mphi stimulate helper T cells in nonresponder parental mice, these observations suggest that distinct subsets of T cells exist in F(1) mice which behave phenotypically as responder and nonresponder parental T cells after immunization with soluble GAT and GAT- Mphi.

Alanine↗
PubMed1981

Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells.

C57BL/10 mice were injected with semiallogeneic (B10.D2 X C57BL/10)F(1) spleen cells via the anterior facial vein within 24 h of birth to induce tolerance to B10.D2 (H-2(d)) alloantigens. Spleen cells from these mice as adults developed reduced, but significant, mixed lymphocyte and cytotoxic lymphocyte responses in vitro to H-2(d) stimulator cells and these treated mice rejected first-set B10.D2 skin grafts within a normal time-course, indicating that at best only a state of partial tolerance had been induced. Spleen cells from these mice failed to develop antibody responses to a variety of antigens in vitro when H-2(d) macrophages were in the cultures. Partially purified T cells from these neonatally treated mice suppressed primary antibody responses by normal syngeneic spleen cells in the presence of H-2(d) but not other allogeneic macrophages. These radiosensitive, haplotype-specific suppressor T (Ts) cells inhibited primary antibody responses by blocking initiation of the response, but failed to suppress secondary antibody responses and mixed lymphocyte or cytotoxic lymphocyte responses by appropriate responding spleen cells. To activate H-2(d) haplotype-specific Ts cells, stimulation with IA(d) subregion antigen(s) was necessary and sufficient; syngenicity at the I-A subregion of H-2 between the activated Ts cells and target responding spleen cell populations was also necessary and sufficient to achieve suppression. Comparable results have been obtained with spleen cells from BALB/c mice injected as neonates with (B10.D2 x C57BL/10)F(1) spleen cells where IA(b) antigens activate the haplotype-specific Ts cells. Implications for the significance of this population of haplotype-specific Ts cells in immune regulation are discussed and the properties of these Ts cells are compared and contrasted with other antigen-specific and nonspecific Ts cells whose activity is restricted by I- region products.

Animals↗
PubMed2003

Response of hematopoiesis to cyclophosphamide follows highly specific patterns in bone marrow and spleen.

Sublethal cyclophosphamide treatment induces unique regeneration patterns in bone marrow and the spleen of a mouse. Colony-forming units spleen (CFU-S)(day 8), CFU-granulocyte-macrophage (GM), nucleated cell counts, and their differentials in bone marrow, spleen, and peripheral blood were determined in mice treated with a single dose of cyclophosphamide. To study further the mechanisms underlying the unique patterns of hematopoietic regeneration after cyclophosphamide, mRNA levels for stem cell factor (SCF), Flt-3 ligand, and macrophage inflammatory factor (MIP)-1 alpha cytokines were determined in bone marrow and spleen. Granulocyte precursor cells were less depleted by cyclophosphamide compared to erythroid nucleated cells and lymphocytes both in bone marrow and spleen. Rapid expansion of granulopoietic cells increased the granulocytic/erythroid ratio significantly during regeneration. CFU-S in the bone marrow and the spleen showed different sensitivity in vivo but not in vitro to cyclophosphamide; CFU-GM were equisensitive in both sites. In bone marrow, an initial fast recovery of CFU-S and CFU-GM on days 2 to 3 was followed by a secondary deep decline in their numbers occurring between days 5 and 7. This decline was accompanied with a depression of CFU-S proliferation and with significantly increased CFU-S numbers in the peripheral blood. In the spleen, absolute CFU-S and CFU-GM numbers were increased several-fold at this time. Seven days after cyclophosphamide, the spleen contained 69% of the total body CFU-S compared to 4% in controls. Splenectomy did not abolish the secondary disease of CFU-S in the bone marrow, but it led to a marked elevation of circulating leukocytes and CFU-S. There was an eight-fold increase in the SCF mRNA level in the bone marrow 2 days after cyclophosphamide, corresponding with a high proliferation rate of CFU-S. No significant changes in mRNAs for Flt-3 ligand and MIP-1 alpha have been found. This in-depth analysis of murine hematopoietic responses to cyclophosphamide provides evidence for the complexity of the involved local and systemic regulations. This represents a significant challenge to experimental hematology, which could now be tackled with methods allowing the study of changes in the gene expression during cyclophosphamide-induced hematopoietic damage.

Aldehyde Dehydrogenase↗
PubMed1989

Sex-dependent, early cytokine production by NK-like spleen cells following infection with the D variant of encephalomyocarditis virus (EMCV-D).

Spleen cell cultures from diabetes-resistant ICR Swiss females exhibited an increase in expression of Ia antigens 24 hours post-infection (PI) with EMCV-D while comparable spleen cell cultures from diabetes-susceptible males of this strain did not exhibit this increase in Ia antigens expression. A monoclonal antibody specific for mouse interferon-gamma (IFN gamma) eliminated this increase in Ia antigens expression. Interferon-gamma (IFN gamma) and interleukin 2 (IL-2) production by EMCV-D-infected spleen cell cultures were monitored at 4-hour intervals for 24 hours. Female spleen cells produced IFN gamma earlier (less than 16 hours PI) and in greater amounts than did comparably treated male spleen cells. Addition of a monoclonal rat anti-mouse IL-2 to virus-infected cultures did not significantly affect the early (less than 16 hours PI) production of IFN gamma by spleen cells of females. Treatment of the spleen cell donors with rabbit anti-asialo GM1 (AAGM1) abolished early production of IFN gamma in virus-infected female spleen cell cultures and reduced the early IL-2 production by infected male and female cells. These results suggest that an NK-like cell is responsible for the early female IFN gamma production; this may be a factor in the resistance of female ICR Swiss mice to EMCV-D-induced diabetes.

Animals↗