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PubMed1991

Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins.

Scrapie-associated fibrils (SAF) and protease-resistant proteins (PrP) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. The spleens of infected animals contained lower levels of infectivity, PrP, and SAF than did brains. Regardless of the route of infection, both SAF and infectivity were detected in spleen before brain. Infectivity increased in brains and spleens of 139A-infected mice before the detection and increase in SAF, suggesting that the synthesis of SAF and PrP may not be the limiting factor in agent replication. In contrast to those in ME7- and 263K-infected animals, the Western blot profiles for PrP from brain and spleen of 139A-infected mice exhibited distinct differences. Results indicate that SAF and PrP found in the spleens are both organ- and scrapie strain-specific.

Animals↗
PubMed1981

Effect of protein deficiency on the lysosomal enzyme activities of the spleen and thymus of weanling rats.

The effect of a low protein (4%) diet on the activity of the hydrolytic enzymes ribonuclease, deoxyribonuclease, acid and alkaline phosphatases, beta-glucuronidase and lysozyme has been studied in the spleen and thymus of weanling Wistar rats. Experimentation was carried out over 20 and 30 days, and comparisons were made with well-nourished (12% protein) controls. Body weight decreased during the terminal period in protein-deficient animals (P less than 0.001). Spleen and thymus absolute net weights also dropped significantly (P less than 0.001). In terms of organ weight relative to body weight, there was a clear decrease in thymus compared with controls (P less than 0.001). Enzyme activities expressed per total organ fell significantly. Thus, in spleen at 20 days the decrease was maximum in ribonuclease activity (91.15%) and minimum in acid phosphatase activity (44.09%). Thymus decreases ranged from 83.60% activity in beta-glucuronidase and 93.56% in ribonuclease. At 30 days decreases were accentuated; the maximum value in spleen was 92.34% lysozyme and, in thymus, 97.09% acid phosphatase. A large increase in hydrolytic activity expressed per milligram of protein was registered, especially at 30 days. This increase reached a maximum of 78.08% beta-glucuronidase in thymus and a minimum of 56.1% alkaline phosphatase; acid phosphatase and ribonuclease activities were not modified. In spleen, however, acid phosphatase (34.00%), alkaline phosphatase (62.50%), deoxyribonuclease (39.25%), and beta-glucuronidase (36.01%) increased, but lysozyme and ribonuclease enzymes decreased. We concluded that a low protein diet increases catabolism in spleen and thymus through an enhancement of lysosomal hydrolase activities.

Acid Phosphatase↗
PubMed1976

The Fv-2r resistance gene in mice: its effect on spleen colony formation by Friend virus-transformed cells.

To determine the mechanism by which the recessive Fv-2r gene confers complete resistance to spleen focus formation and to the induction of early splenomegaly characteristic of the Friend virus (FV) disease syndrome, we compared the parameters of FV infection in susceptible DBA/2 (D2) (Fv-1n, Fv-2s) and partially congenic D2.Fv-2r (Fv-1n, Fv-2r) mice. After infecting these mice with N-tropic FV complex, we followed the replication of spleen focus-forming virus (SFFV) and the generation of SFFV-transformed tumor colony-forming cells (CFC) in their spleens. By both parameters D2.Fv-2r mice were 20- to 100-fold less susceptible than DBA/2 controls, but the inhibition was only partial. Transplantation of washed spleen cells from SFFV-infected DBA/2 mice resulted in equal growth and recovery of tumor CFC from both D2.Fv-2r and Fv-2s mice. However, these tumor cells grew as colonies in Fv-2s mice, whereas they grew diffusely in the spleens of D2.Fv-2r hosts and did not develop into macroscopically or microscopically visible colonies. Thus the completeness of the resistance to spleen focus formation that defines the Fv-2r gene was reflected only in the complete suppression of the colonial growth of tumor cells, whereas the other parameters of infection showed no or only partial inhibition.

Animals↗
PubMed1996

Galectin-1 from bovine spleen: biochemical characterization, carbohydrate specificity and tissue-specific isoform profiles.

Selected biochemical properties, including the charge heterodispersity profile and carbohydrate specificity, of bovine galectin-1 were determined in detail. The lectin was purified through an improved purification protocol that yielded 35-40 mg/kg of wet tissue with a specific activity of 1.7-2 x 10(4) mg-1.ml. The galectin is a homodimer of approximately 14.5 kDa subunits with E(280)mg/ml of 0.65 ml.mg-1.cm-1. When stored in the presence of its carbohydrate ligand, the lectin's binding activity remained stable in a non-reducing environment even at room temperature. The optimal pH for binding to the ligand was 6.5-8.0. The overall carbohydrate specificity of the bovine galectin-1 isolated from spleen is similar to that of the galectin isolated from heart and to other mammalian galectins that exhibit "conserved" (Type I) carbohydrate recognition domains (CRDs) [Ahmed, H. and Vasta, G.R. (1994) Glycobiology 4, 545-549], but differs from those from Xenopus laevis and rat intestine domain I. The fluorescence of 4-methylumbelliferyl alpha-D-galactopyranoside was quenched on binding to bovine spleen galectin-1. Scatchard plots of data obtained at 5, 15, and 30 degrees C showed that the galectin has two sugar exothermic binding sites with association constants of 3.4 x 10(5), 1.0 x 10(5), and 0.3 x 10(5), respectively. Chemical modification studies indicated that histidine, tryptophan, carboxylic acid, and arginine, but not lysine or tyrosine, are involved in the binding to the carbohydrate ligand. On isoelectric focusing, the spleen galectin-1 appeared as six isoforms ranging from pI4.56-4.88 with main components at pI 4.63 (34.0%), 4.73 (42.6%), and 4.88 (16.6%). The galectin-1 isolated from heart yielded a quali- and quantitatively different profile with four isoforms ranging from pI 4.53-4.73, those with pIs of 4.56, 4.63, and 4.73 being common to the spleen homolog. Edman degradation of selected peptides purified from the spleen galectin-1 digest revealed amino acid sequences identical to those obtained for the heart galectin-1. This suggests that although point mutations in the subunit primary structure may not be the likely source of isolectins, as observed for X. laevis, tissue-specific co- or post-translational modifications may be the possible cause of the differences in the galectin isoform profile between bovine spleen and heart.

Amino Acid Sequence↗
PubMed1997

Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes from rat thymus and spleen.

In the present work we analyze by reverse transcription, polymerase chain reaction, cDNA cloning, and sequence analysis the expression of membrane melatonin receptors in rat thymus and spleen. Results show, for the first time, that the melatonin receptor mRNA is expressed in both the thymus and spleen. Moreover, the melatonin receptor mRNA was expressed in all the lymphocyte subpopulations (CD4+,CD8+, double positive, double negative, and B cells) studied from the rat thymus. The Southern blot analysis with the melatonin receptor probe and sequence data also showed the identity of the DNA fragments in thymus, spleen, and the lymphocyte subpopulations studied. The melatonin receptor fragments amplified from rat brain, thymus, and spleen share identical nucleotide sequences with the rat Mel1a-melatonin receptor subtype. No signal was obtained with primers used to amplify the rat Mel1b-melatonin receptor subtype in both thymus and spleen. Finally, the melatonin receptor mRNA transcript distribution throughout the rat thymus was examined. Using digoxigenin-labeled cRNA probe to the specific melatonin receptor mRNA, examination of the whole thymus revealed a clear hybridization signal in both cortex and medulla. Melatonin receptor gene expression in the thymus and spleen supports the notion of the immunomodulatory role of melatonin.

Animals↗
PubMed1998

Comparative analysis of murine dendritic cells derived from spleen and bone marrow.

In order to improve upon preclinical tumor vaccine strategies that employ dendritic cells (DC), we now have compared short-term cultures of spleen- and GM-CSF/IL-4-stimulated bone marrow (BM) to determine if differences exist in phenotype and function of murine DC derived from primary and secondary hematolymphoid organs. Although cultures of BM contained a lower percentage of DC compared to spleen, their capacity to stimulate a primary allogeneic mixed leukocyte reaction (MLR) and to uptake fluorescent dextran was substantially greater. In addition, the overall yields of DC per animal was at least twofold greater from BM compared to spleen. Cultures of BM harvested at day 3, 6, or 9 stimulated comparable levels of primary allo-MLR on a per-cell basis. However, there was a consistent loss (at least twofold) of all cells occurring beyond day 6 as compared with cell yields from earlier time points. Importantly, we also improved on methods to rapidly obtain highly enriched DC (> 90%) from BM, which has obviated the reported prior need for complex antibody and complement treatments to remove contaminating mature T and B lymphocytes, Ia-bearing cells, and granulocytes before DC generation. In contrast, although similar purity of DC with similar phenotype and function could be obtained from the spleen, substantial loss in yield occurred, suggesting a further difference in DC between the two tissue sources. The overall yield of DC derived from spleen and BM cultures could be substantially increased by in vivo pretreatment of the donor animals with recombinant Flt3-L. Collectively, these studies demonstrate that notable differences exist in DC preparations derived from spleen vs. BM and that BM provides the preferred source of DC that can be rapidly enriched to high purity for use in further vaccine development.

Adjuvants, Immunologic↗
PubMed2005

Importance of Tc-99m sulfur colloid liver-spleen scans performed before indium-111 labeled leukocyte imaging for localization of abdominal infection.

INTRODUCTION: The localization of intraabdominal abscesses is a difficult imaging problem in nuclear medicine, especially when the location of the abscess is in the area of the liver and spleen. The need for performing Tc-99m sulfur colloid liver-spleen scans before injecting indium-111 leukocytes for improved lesion detection and characterization versus performing In-111 leukocyte scans alone has been questioned in the literature MATERIALS AND METHODS: We present 3 patients with intraabdominal abscesses in the liver-spleen area, in which liver-spleen scans were performed before In-111 leukocyte scans. The findings of all were correlated with computed tomography and interventional procedures. RESULTS: In all patients, the Tc-99m liver-spleen scan helped for accurate recognition of the location of the abscess, correlated with computed tomography findings, and were helpful for intervention and exclusion of the other sources of infection. CONCLUSION: Data from these 3 patients reinforces the need for Tc-99m sulfur colloid liver-spleen scans before performing In-111 WBC scans for better localization and interventional treatment of intraabdominal abscesses.

Abdominal Abscess↗
PubMedDate not supplied

Immunoglobulin synthesis by cultured lymphocytes from spleen and mesenteric lymph nodes after thermal injury.

A 30% burn injury has been previously reported to impair mitogenic response of splenocytes to a B-lymphocyte mitogen and to affect serum levels of serum class-specific immunoglobulin. To further investigate the effect of burn injury on the function of B lymphocytes in gut-associated and systemic immune tissues, we studied class-specific immunoglobulin synthesis by cultured lymphocytes from spleen and mesenteric lymph nodes after burn injury in rats. Male Lewis rats received 30% full-thickness burn injuries, and 4 days later, the animals were killed to remove spleen and mesenteric lymph nodes. The cells from spleen and mesenteric lymph nodes were cultured for 5 days with 25 micrograms/ml of lipopolysaccharide. Concentrations of immunoglobulin G (IgG), IgM, and IgA in the supernatant of each well were then measured with enzyme-linked immunosorbent assay for class-specific immunoglobulin. Synthesis of IgG by lymphocytes from spleen was statistically significantly impaired by burn injury (p less than 0.05), but synthesis of IgG by lymphocytes from mesenteric lymph nodes was not affected. There were no significant differences in IgM and IgA synthesis by lymphocytes from spleen between burned animals and controls. The immunoglobulin synthesis in mesenteric lymph nodes did not differ significantly in burned animals compared with controls. The impaired IgG synthesis by lymphocytes from spleen may contribute to increased risk of infection after burn injury.

Animals↗
PubMed1982

Functional assessment of hepatocytes after transplantation into rat spleen..

The retention of structural integrity and metabolic function by isolated hepatocytes after ectopic transplantation has been investigated in autografted rats. Rats were partially hepatectomized and isolated hepatocytes prepared from the excised liver lobes were implanted into their spleens. Histological examination of the spleens 7 or more weeks after implantation revealed aggregates of hepatocytes in the red pulp. Two tests of biochemical function were applied to the hepatocytes after transplantation. In the first the hepatobiliary imaging agent technetium-99m N-[N'-(2, 6-dimethylphenyl)carbamoylmethyl]iminodiacetic acid (99mTc HIDA), which was shown to be avidly taken up by isolated hepatocytes in vitro, was infused into the tail veins of autograft and control rats. Radioactivity accumulating in the spleens of autografted rats was markedly greater than that in controls implanted with lethally damaged cells or in nontransplanted rats. In the second the presence of bilirubin metabolites was sought in autograft spleens after intravenous infusion of bilirubin. Both mono- and diglucuronides of bilirubin were recovered from the spleens of autograft rats but no conjugates were recovered from the spleens of unoperated controls. We conclude that after autotransplantation isolated hepatocytes retain their morphology and at least some of their functional activities.

Animals↗
PubMed1983

Further characterization of macrophage adsorption of suppressor cell activity from tumor-allosensitized spleen.

Suppressor cell activity from P815-allosensitized C57BL/6 spleen can be decreased by incubating the tumor-allosensitized spleen cells on monolayers of thioglycollate-stimulated BDF1 peritoneal macrophages for 2 or 4 hr. The adsorption response appears to be specific for macrophages, because adsorption of suppressor cell activity does not occur following incubation of P815-allosensitized spleen cells on confluent monolayers of mouse spleen cells or mouse embryonic fibroblasts. Pretreatment of macrophage monolayers with X irradiation (2,000 rads) or anti-Thy 1.2 serum (and complement) does not affect their ability to bind suppressor cell activity. Adsorption of suppressor cell activity from P815-allosensitized spleen can also be carried out by proteose peptone-stimulated or Corynebacterium parvum-stimulated macrophages. Blockage of macrophage Fc receptors decreases the ability of thioglycollate-stimulated macrophages to adsorb suppressor cell activity. Monolayers of P815 or P388 cells, two cell types positive for Fc receptors, are unable to adsorb suppressor cell activity from the tumor-allosensitized spleen. The significance of our findings is discussed in terms of the relationship between macrophages and suppressor cells in the immune response to normal or tumor allografts.

Adsorption↗
PubMed1988

The in vivo immunosuppressive action of suppressor cells from alloantigen-cyclosporine-treated mice and the capacity of spleen cells to release interleukins and gamma-interferon.

Antigen-nonspecific suppressor T cells were identified in spleens of mice rendered unresponsive by sensitization of allogeneic antigen in combination with cyclosporine (CsA) treatment. Suppressor cells were obtained from C57BL/6 (B6, H-2b) mice treated with a single i.p. injection of 1 x 10(7) allogeneic P815 (H-2d) cells combined with a five-day course of CsA, a group that did not show any cytotoxic activity of spleen cells against P815 targets. These noncytolytic spleen cells displayed suppressor activity on the induction of cytotoxic T (Tc) cells of normal lymphocytes against not only P815 stimulator (80.9% suppression, P less than 0.01, responder:additional cell ratio = 2.5:1) but also third-party BW5147 (H-2k) stimulator (68.2% suppression, P less than 0.01). The unresponsive state appears to be due to suppressor T (Ts) cells that are nonadherent to plastic or nylon-wool, 1500 rads-sensitive, and Thy-1-positive. Capacities of spleen cells from CsA-P815-treated mice to release cytokines (interleukin 1 [IL-1]), interleukin 2 [IL-2], interleukin 3 [IL-3], and gamma-interferon [gamma-IFN]) were examined. Spleen cells from CsA-P815-treated B6 mice displayed 84.1%, 91.7% and 90.8% inhibition (0.35 +/- 0.07 U/ml, 1.4 +/- 0.29 U/ml, and 7.0 +/- 0.9 U/ml) of IL-1, IL-2, and gamma-IFN production compared with normal mice (2.2 +/- 0.54 U/ml, 16.9 +/- 2.1 U/ml, and 76.0 +/- 3.1 U/ml, P less than 0.01), respectively. However, IL-3 production was significantly less inhibition (46.1%, 2.35 +/- 1.0 U/ml in CsA-P815-treated mice and 4.36 +/- 1.7 U/ml in normal mice) compared with other cytokines (IL-1, IL-2, gamma-IFN). Two systems were employed to assess the immunosuppressive efficacy of antigen-nonspecific Ts cells in vivo. First, adoptive transfer (i.p.) of spleen cells harvested from CsA-P815-treated mice ten days after treatment on 3 consecutive days (days 0, 1, 2) at a 3 x 10(7) cell dose into virgin B6 mice that were immunized with P815 cells (1 x 10(7), day 0) completely inhibited the development of Tc cells against P815 targets (5% specific cytolysis, effector:target ratio [E:T] = 200). The suppressor effect was immunologically nonspecific; adoptive transfer of Ts cells from CsA-P815-treated mice also abrogated the development of Tc cells against third=party BW5147 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Differential effect of cyclosporine in vivo on the distribution of T cell subsets in the thymus, spleen, and lymph nodes.

Cyclosporine treatment of BALB/c mice (at a dose of 20 mg/kg every other day for 3 weeks) caused a remarkable reduction in the PNA-, L3T4+Lyt-2- subset of thymocytes. A significant reduction of the L3T4+Lyt-2-subset was also observed in both the lymph node and spleen cells of CsA-treated mice, though the degree of the reduction was lower than that in thymocytes. Both lymph node and spleen cells from CsA-treated mice showed a significant increase in the percentage of Thy-1.2 negative, L3T4-Lyt-2- cells (perhaps B cells). Thymocytes from CsA-treated mice showed a reduction in the in vitro proliferative responses to Con A and PHA. On the other hand, there was a slight, but not significant, decrease in the responses of lymph node cells to Con A, PHA and LPS. Spleen cells from CsA-treated mice showed a significant reduction in the responses to Con A and PHA, though the degree of the reduction was lower than that of thymocytes. There was a significant decrease in the proliferative response of spleen cells to LPS. These results suggest that CsA affects both thymus and spleen cells in vivo, preferentially impairing the L3T4+Lyt-2- subset (helper T cells or their precursors) within the thymus. The lymph node cells seem to be relatively spared from the in vivo effect of CsA compared with cells in the thymus and spleen.

Animals↗
PubMed1989

Natural suppressor cells derived from adult spleen and thymus.

Natural suppressor (NS) cell lines were derived from the spleen and thymus of adult mice using procedures previously used to derive NS cells from neonatal spleen. Adult spleen-derived NS cells showed slightly greater suppression of the MLR than neonatal spleen-derived NS cells, and thymus-derived NS cells showed the least suppression. Adult spleen-derived NS cells prevented death from lethal GVHD when administered to sublethally irradiated weanling mice that received an otherwise lethal GVHD provoking inoculum. The stable cell surface phenotype of adult tissue-derived NS cells was similar to that previously described for neonatal and TLI spleen-derived NS cells: strongly positive for Thy 1.2, Ly-5, and asialo-GM1 antigens while negative for Ly-1, Ly-2, L3T4, MAC-1, and surface immunoglobulin.

Aging↗
PubMed1992

Lack of evidence that a transplanted liver causes acute graft-versus-host disease in rats. A comparison of liver and spleen grafts.

In this study, we used rat transplant models to investigate whether--and, if so, to what extent--transplanted liver had the potential to incite graft-versus-host disease, compared with the disease induced by a spleen graft. Livers from PVG(RT1c) rats were transplanted orthotopically into (DAxPVG)F1 (RT1a/c) rats and vascularized spleen grafts from PVG rats were transplanted heterotopically into (DAxPVG)F1 recipients. The intensity of the GVH disease was assessed by the recipients' morbidity and mortality, recipient-type serum class I (RT1Aa) antigen titer, and histological examination. The recipients of spleen grafts died within 14 and 23 days of transplantation; all animals had lost body weight and showed typical GVH signs, such as ear erythema, diarrhea, and alopecia. However, all the recipients bearing liver grafts survived indefinitely and did not demonstrate weight loss or the typical symptoms associated with GVH disease. The skins, tongues, and intestines of the liver-grafted rats were virtually normal at histological examination, whereas the livers, salivary glands, and skins of spleen-grafted rats were infiltrated by immunoblasts. The recipient-type serum RT1Aa antigen titer increased progressively until death in the spleen graft but not the liver graft recipients. These results provide evidence that suggest that transplanted liver is less likely than transplanted spleen to initiate the GVH disease in rats.

Acute Disease↗
PubMed1996

Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow.

SCID mice are resistant to intraperitoneal infection with 10(3) and 10(4) intracerebral ID50 units of ME7 scrapie agent whereas they develop disease after intracerebral challenge. However, higher doses introduced, by intraperitoneal or subcutaneous routes, produce disease. Immunocompetent mice of the same strain (CB20) developed scrapie following either intracerebral or intraperitoneal infection. Bioassay of spleens from SCID mice infected with 10(-1) dilutions of ME7 scrapie by intraperitoneal, intracerebral or abdominal subcutaneous injection showed traces or low levels of infectivity in spleen. However, subcutaneous injection beneath the skin of the neck failed to infect the spleen. CB20 bone marrow reconstitution of SCID mice resulted in the regeneration of a normal lymphoid architecture in the spleen. Spleens from these reconstituted mice, infected intracerebrally with a 10(-1) dilution of ME7 contained high levels of infectivity. These results suggest that the ability to replicate scrapie agent in spleen or lymphoid tissue depends on the restoration of normal lymphoid structure and in particular the presence of differentiated follicular dendritic cells. The possibility that SCID mice can select minor strains of scrapie which are normally unrecognized in cloned ME7 is discussed.

Animals↗
PubMed1981

Routine laboratory tests in relation to spleen size and tumour involvement in untreated Hodgkin's disease.

A number of routine laboratory tests were studied in 39 untreated patients with Hodgkin's disease with respect to size and tumour involvement of the spleen. Eighteen patients with tumour-engaged spleens had lower total lymphocyte counts and IgG and IgM levels than patients with non-involved spleens. However, no significant differences in these respects were found between patients with tumour-involved spleens weighing less than 500 g and patients without splenic tumour involvement. Hemoglobin values were inversely and reticulocyte counts positively correlated with the weight of involved spleens. Remaining laboratory variables under study, e.g. total granulocyte counts, platelet counts, ESR and liver enzymes, were not associated with the size or tumour involvement of the spleen. It may be concluded that routine laboratory tests yield no specific information as to splenic tumour involvement or size.

Adolescent↗
PubMed1975

Nonspecific elicitation of antibody-forming cells in the mouse spleen by bacterial lipopolysaccharide.

Mechanisms of nonspecific elicitation of anti-sheep erythrocyte (SRBC) hemolytic antibody plaqueforming cells (PFC) in mouse spleens with an injection of bacterial endotoxin (lipopolysaccharide (LPS)) were studied in comparison with the genesis of naturally occurring "background" PFC in normal mouse spleens and of rapidly arising PFC in mouse spleens after immunization with SRBC. The cytokinetic pattern of anti-SRBC PFC response after an injection of LPS was quite different from that of the response elicited after immunization with SRBC. In addition, even though LPS nonspecifically elicited anti-SRBC PFC response in mice, LPS could not confer any immunological memory on mouse immunocytess for a "secondary-type" anti-SRBC PFC response to restimulation with LPS or SRBC. The administration of rabbit anti-mouse thymocyte immunoglobulin or anti-SRBC antiserum in mice markedly suppressed the PFC response after immunization with SRBC, but did not do so after stimulation with LPS. Neonatally thymectomized mice could still respond to stimulation with LPS, producing anti-SRBC PFC in their spleens. Injections of actinomycin D or cyclophosphamide into mice resulted in obvious reductions of the PFC responses elicited by either LPS or SRBC. However, injections of these immunosuppressive antisera or drugs did not affect the number of anti-SRBC PFC in normal mouse spleens. These results suggest that the genesis of anti-SRBC PFC developed under different conditions, i.e., background PFC, LPS-stimulated PFC, and antigen-stimulated PFC, are quite different from each other, and that the nonspecific elicitation of anti-SRBC PFC by LPS does not require the helper function of T lymphocytes. No obvious difference, however, was observed in the time of ontogenic maturation among these three different anti-SRBC PFC in the mouse spleens judging from when they were first manifested after birth.

Animals↗
PubMed1982

Effect of anti-Ia serum in vitro on lipopolysaccharide-induced proliferative responses of murine bone marrow and spleen cells.

The in vitro proliferative response of murine bone marrow cells and spleen cells to bacterial lipopolysaccharide (LPS) and the effect of anti-Ia serum on the response were studied. The incorporation of [3H]thymidine into cells prepared from bone marrow increased in the presence of LPS, but the addition of anti-Ia serum to the cultures reduced the incorporation. Pretreatment of bone marrow cells with anti-Ia serum and complement did not abolish the ability of the cells to respond to LPS, while the same pretreatment destroyed this ability in spleen cells. These results suggest that cultures of Ia-negative bone marrow cells generate Ia-positive cells during the culture period, and the Ia-positive cells are responsive cells to LPS. The proliferative response of 1- or 2-week-old spleen cells was easily suppressed by anti-Ia serum when compared with that of 4-week-old spleen cells. Furthermore, the responses of spleen cells obtained from gamma-irradiated and syngeneic bone marrow cell-reconstituted mice were prominently suppressed by anti-Ia serum in comparison with that of normal adult spleen cells. These findings suggest that LPS-responsive lymphocytes in the developmental stage are quite sensitive to anti-Ia serum. The effect of anti-Ia serum on the maturation of bone marrow-derived lymphocytes was discussed.

Animals↗