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PubMed2000

Fish oil diet affects on oxidative senescence of red blood cells linked to degeneration of spleen cells in mice.

The effect of dietary polyunsaturated fatty acids and alpha-tocopherol supplementation on erythrocyte lipid peroxidation and immunocompetent cells in mice was studied comparatively using seven dietary oils (15% oil/diet, w/w) including fish oil rich in eicosapentaenoic acid (EPA, 20:5, n-3) and docosahexaenoic acid (DHA, 22:6, n-3). A 43% increase in spleen weight, about twice as many spleen cells and no change in the subpopulations of spleen cells, as well as a significant depression of mitogen-induced blastogenesis of both T and B cells in the spleen were observed in mice fed fish oil for 30 days in comparison with soybean oil diet-fed mice. In the fish oil diet-fed mice, membranous lipid hydroperoxide (hydroperoxides of phosphatidylcholine and phosphatidylethanolamine) accumulation as a marker of oxidative senescence in red blood cells (RBC) was 2.7-3.5 times higher than that in mice fed soybean oil, although there was no difference in the plasma phosphatidylcholine hydroperoxide concentration. In spite of the supplementation of alpha-tocopherol to up to 10 times the level in the basal diet, the degeneration of spleen cells and the stimulated oxidative senescence of RBC found by the fish oil feeding could not be prevented. The results suggest that oral intake of excess polyunsaturated fatty acids, i.e. EPA and DHA, in a fish oil diet can lead to acceleration of membrane lipid peroxidation resulting in RBC senescence linked to the lowering of immune response of spleen cells, and that supplementation of alpha-tocopherol as antioxidant does not always effectively prevent such oxidative degeneration as observed in spleen cells and RBC in vivo.

Animals↗
PubMed2002

Spleen and liver pigmented macrophages of Rana esculenta L. A new melanogenic system?

The present study reports the results of a morpho-functional analysis of spleen pigmented cells from Rana esculenta L. and comparison with liver melanin-synthesizing cells, belonging to the macrophage cell lineage. Cytological and cytochemical analyses show that parenchymal pigmented cells of the spleen, like those of the liver, are positive to peroxidase and lipase reactions and have phagocytic properties. The observation of premelanosomes in various stages of differentiation, together with the demonstration of dopa oxidase activity in the melanosome proteins, indicate that spleen pigmented macrophages have endogenous melanogenic ability as do liver pigmented macrophages. Attempts to demonstrate tyrosinehydroxylase activity in melanosome protein extracts from frog spleen and liver, using the same protocol as for mammalian tyrosinases, gave negative results. As regards the dopa oxidase activity revealed, some of its properties differ from the typical behaviour observed for tyrosinases from different sources. Peroxidase activity is shown in spleen and liver melanosome proteins with p-phenylenediamine-pyrocatechol (PPD-PC), and not with typical peroxidase substrates. Suitable inhibition tests revealed that dopa oxidase and peroxidase activities might be supported by two different proteins. Liver melanosome extracts display a very strong laccase (dimethoxyphenoloxidase) activity but spleen extracts do not. Differences observed in the enzymatic properties of the spleen and liver melanosomes suggest that pigmented macrophages may undergo tissue-specific differentiation. These preliminary data show that the melanin pathway of pigmented macrophages is different from that of melanocytes and may pave the way to identification of a new melanogenic pathway in vertebrates.

Animals↗
PubMed1985

In vivo detection and partial characterization of effector and suppressor cell populations in spleens of mice with large metastatic fibrosarcomas.

The MC-2 fibrosarcoma, which is a transplantable tumour syngeneic for BALB/c mice, metastasizes to lymph nodes draining subcutaneous inoculation sites, and also to the lungs. T cell-mediated immunity was detected in Winn assays using spleens from excision immunized mice. T cell-mediated anti-tumour immunity was also detected in spleens from mice with small tumours but disappeared as the tumour burden increased. Protective immune spleen cell activity in the Winn assay was inhibited by prior addition of spleen cells from mice with large tumours, causing increased tumour incidence. Splenic metastases occasionally occurred in the MC-2 model, but were not demonstrable by bioassay in any of the experiments detecting splenic suppressor cell activity. In vivo protective activity was restored to advanced-stage tumour-bearer spleens by whole-body ionizing irradiation (0.5 and 2.5 Gy) of donor mice 15 h before sampling. Spleen cells from mice with small tumours remained protective after 1.5, 2.5 and 4.0 Gy of irradiation in vivo. These results are consistent with the properties of radiosensitive suppressor T cells. In contrast to reports in other tumour models, suppressor cells were not detected until late in the course of MC-2 development. This is surprising in view of the aggressively metastatic nature of MC-2. It is postulated that modulation of the anti-tumour immune response by the suppressor cells is associated with metastasis in this tumour model. The late appearance of both suppressor cells and metastatic cells in the spleen may reflect similar processes occurring earlier in regional lymph nodes.

Animals↗
PubMed1997

Activation by high potassium of a novel voltage-operated Ca2+ channel in rat spleen.

1. High potassium produced a concentration-dependent contraction in rat isolated spleen. 2. The high potassium-induced contraction of rat spleen was abolished in Ca(2+)-free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca2+ restored the high potassium-induced contraction to the control level. 3. Nifedipine, verapamil, diltiazem, Cd2+, Ni2+, Co2+, R-(+)-Bay K 8644 and pimozide inhibited and relaxed high potassium-induced contraction of rat spleen with IC50 and EC50 values much higher than those values in rat aorta. 4. In addition, high potassium-stimulated contraction of rat spleen was insensitive to omega-conotoxin GVIA, omega-conotoxin MVIIC and omega-agatoxin IVA. 5. The high potassium-induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3-tropanyl-indole-3-carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX), L-659,877, L-703,606, lorglumide, PD 135,158 N-methyl-D-glucamine, benextramine, amiloride, dantrolene, TMB-8, econazole, staurosporine and neomycin. 6. Forskolin and sodium nitroprusside relaxed high potassium-induced contraction of rat spleen with EC50 values of 0.55 +/- 0.04 and 20.0 +/- 2.7 microM, respectively. 7. It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage-operated Ca2+ channel in rat spleen.

Animals↗
PubMed1980

Fluid endocytosis by rat liver and spleen. Experiments with 125I-labelled poly(vinylpyrrolidone) in vivo.

1. Rates of fluid endocytosis of rat liver, spleen, hepatocytes and sinusoidal liver cells have been determined, by using 125I-labelled poly(vinylpyrrolidone) as marker. Poly(vinylpyrrolidone) was injected intravenously into rats, and plasma clearance and uptake by liver and spleen were estimated. From these data, rates of fluid endocytosis of 1.2 and 1.8 ml of plasma/g of protein per day were calculated for liver and spleen respectively. Essentially the same results were found in nephrectomized rats. 2. Hepatocytes and sinusoidal cells were separately isolated by the collagenase/Pronase method, and sinusoidal cells were further fractionated by centrifugal elutriation. Hepatocytes, sinusoidal cells, Kupffer cells and endothelial cells showed rates of fluid endocytosis of 0.96, 9.0, 19 and 13 ml of plasma/g of cell protein per day respectively. Total-body X-irradiation did not influence uptake of poly(vinylpyrrolidone) by spleen, indicating that spleen lymphocytes are not significantly involved in fluid endocytosis. 3. For liver a rate constant of exocytosis of 5% per day was found, whereas for spleen no significant loss of accumulated label could be demonstrated during a 21-day period. 4. Distribution of label over a great number of organs and tissues was measured 9 days after the injection. Liver, skin, bone and muscle together contained about 70% of the label present in the carcass; only spleen and lymph nodes contained more label per g fresh weight of tissue than liver.

Animals↗
PubMed1994

Application of simultaneous spleen and liver perfusion to the study of reverse cholesterol transport.

1. A new method to isolate and perfuse the rat spleen and liver simultaneously with a common blood perfusate at high haematocrit was developed. The spleen was pre-labelled with [3H]cholesterol, enabling reverse cholesterol transport from an extrahepatic tissue to the blood and thence to the liver and bile to be studied in a single preparation in vitro. 2. The presence of the liver significantly increased the release of [3H]cholesterol from the spleen by 15%, compared with experiments where the spleen was perfused alone. 3. There was a substantial release of [3H]cholesterol and cholesterol mass from the spleen to serum lipoproteins, the majority (80%) to high-density lipoprotein (HDL), in which cholesteryl ester accumulated. 4. The HDL subfractions HDL2 and HDL3 (d 1.085-1.250) were most important for removal of cholesterol from the spleen, whereas HDL1 and HDL2 (d 1.050-1.125) were important for delivery of cholesterol to the liver, a net uptake of cholesteryl ester occurring only from these fractions. 5. Approximately half of the [3H]cholesterol released by the spleen was recovered in erythrocytes. Also, in experiments utilizing a lipoprotein-free perfusate containing erythrocytes, a substantial quantity of [3H]cholesterol was transported and/or exchanged into the liver and bile, indicating that erythrocytes play an important role in the equilibration of unesterified cholesterol between the tissues.

Animals↗
PubMed1999

Changes in T-lymphocyte subsets in lungs and spleens of mice with slowly progressive primary mycobacterium tuberculosis infection: involvement of unconventional T-cell subsets.

Our previous study showed that the cell-activation responses and cytokine-secretion patterns were different in lungs and spleens of mice with slowly progressive primary Mycobacterium tuberculosis infection. The aim of the present study was to characterize the T-cell subsets in lungs and spleens of mice with a similar infection. The percentages of T-cell subsets were determined by flow cytometry and the absolute numbers were calculated. Spleens of infected mice showed a threefold expansion of CD4+ cells but no change in CD8+ cells, whereas lungs had a threefold increase of both subsets. A significant expansion of CD4-CD8-alphabeta+ [double negative (DN)alphabeta+] subsets was observed in the lungs of infected mice compared with uninfected mice. This was not the case in the spleens of infected mice. In infected mice the CD4-CD8- (DN) population preferentially expressed alphabeta-T-cell receptors (TCR) in the lungs but gammadelta-TCR in the spleens. The percentages of many T-cell subsets were significantly higher in the lungs than in the spleens of both uninfected and infected mice. However, the percentages of CD4+ and CD4-CD8+TCR- subsets in the lungs were significantly lower than in the spleens of infected mice. We also observed some previously unreported T-cell subsets: double positive-TCR- (DPTCR-), DPalphabeta+ and DPgammadelta+. So far their functions are unknown.

Animals↗
PubMed2002

Differential expression of cytokines (IL-2, IFN-gamma, IL-10) and adhesion molecules (VCAM-1, LFA-1, CD44) between spleen and lymph nodes associates with remission in chronic relapsing experimental autoimmune encephalomyelitis.

We have recently established chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) in SJL mice with a modified protocol. In this model, splenectomy aborts the relapsing-remitting course of the disease, and adoptive transfer of lymphocytes of the local draining lymph nodes (LNs) to naive recipients exacerbates the disease. Adoptive transfer of splenic cells converted acute EAE into CR-EAE in the naive recipients. In light of the different roles of the spleen and LNs in the evolution of CR-EAE, we examined by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) whether a differential mRNA expression profile of cytokines and cellular adhesion molecules (CAMs) in spleen versus LN was associated with relapse or remission in CR-EAE. All the cytokines tested (interleukin-1beta (IL-1beta), IL-2, IL-4, IL-7, IL-10, interferon-gamma (IFN-gamma)) as well as CAMs (ICAM-1, ICAM-2, VCAM-1, LFA-1 and CD44) were expressed at substantial levels in both spleen and LNs. Interestingly, disease remission was found to be associated with an increased mRNA expression of IL-2 and IFN-gamma in LNs and a decreased IL-10 mRNA level in the spleen. On the other hand, an increased mRNA expression of VCAM-1, LFA-1 and CD44 was observed in the spleens in comparison with that in LNs of mice, with remission. During relapses, mRNA expression of the tested molecules did not significantly differ between spleens and LNs. Our results suggest that a differential and polarized expression profile of certain cytokines and CAMs in spleen versus LN could provide molecular correlates of the cyclic pathogenesis of CR-EAE.

Animals↗
PubMed2004

[Accessory spleens--diagnostic and therapeutic problem of the laparoscopic splenectomy in idiopathic thrombocytopenic purpura patients].

The preoperative detection of accessory spleens (AS) is essential in ITP patients. The aim of this study was to evaluate the reasons of failure and long-term results of laparoscopic splenectomy (LS) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-four ITP patients (27 females and 7 males) underwent LS between June 1998 and January 2001. Computed Tomography (CT) and sonography (US) were performed preoperatively to evaluate the size of the spleen and to detect the presence of possible accessory spleens which were found in two cases. AS were seen during laparoscopy in three cases. During follow-up (median time = 23 months), in three patients a low platelet count was seen after 5 months, 1.5 and 1.8 years pop. In all these cases scintigraphy was performed, which revealed in one case the residual accessory spleen. In the two other patients, inspite of thrombocytopenia no residual spleens were found. The authors conclude that laparoscopic splenectomy is a safe and effective procedure in patients with ITP. The problem of accessory spleens can be managed by careful videoscopic examination of the abdominal cavity during splenectomy. The use of the preoperative imaging techniques for detection of accessory spleens is limited by the insufficient sensitivity of the examination.

Adolescent↗
PubMed1995

[Quantitative computed tomographic determination of spleen size to assess the course of malignant lymphomas].

The purpose of this study was to correlate CT-assessed spleen indices (length x width x depth) and their changes under therapy or in the follow-up, with the clinical course and morphological changes. In 66 patients with 200 CT's of the abdomen the spleen index was calculated and 134 spleen index differences (delta SI) were correlated with the clinical outcome. The normal group showed a mean of delta SI of -8 = 112, equivalent boundaries of -120 and 104. delta SI of progressive lymphomas (n = 32) was 313 (p < 0.01). In 10/14 patients of this group, morphological signs of infiltration were found. In regressive lymphomas (n = 63) we found delta SI = -211 (p < 0.001). 23/29 with delta SI < -120 showed signs of spleen involvement in the preliminary examination. Since there are only slight intraindividual changes of CT-assessed spleen indices and a good correlation of spleen index differences with the clinical outcome. the spleen index is a useful instrument in the follow-up of malignant lymphomas.

Disease Progression↗
PubMed2001

Effects of forced diving on the spleen and hepatic sinus in northern elephant seal pups.

In phocid seals, an increase in hematocrit (Hct) accompanies diving and periods of apnea. The variability of phocid Hct suggests that the total red cell mass is not always in circulation, leading researchers to speculate on the means of blood volume partitioning. The histology and disproportionate size of the phocid spleen implicates it as the likely site for RBC storage. We used magnetic resonance imaging on Northern elephant seals to demonstrate a rapid contraction of the spleen and a simultaneous filling of the hepatic sinus during forced dives (P < 0.0001, R(2) = 0.97). The resulting images are clear evidence demonstrating a functional relationship between the spleen and hepatic sinus. The transfer of blood from the spleen to the sinus provides an explanation for the disparity between the timing of diving-induced splenic contraction ( approximately 1-3 min) and the occurrence of peak Hct (15-25 min). Facial immersion was accompanied by an immediate and profound splenic contraction, with no further significant decrease in splenic volume after min 2 (Tukey-Kramer HSD, P = 0.05). At the conclusion of the dive, the spleen had contracted to 16% of its predive volume (mean resting splenic volume = 3,141 ml +/- 68.01 ml; 3.54% of body mass). In the postdive period, the spleen required 18-22 min to achieve resting volume, indicating that this species may not have sufficient time to refill the spleen when routinely diving at sea, which is virtually continuous with interdive surface intervals between 1 and 3 min.

Animals↗
PubMed2003

Effect over time of in-vivo administration of the polysaccharide arabinogalactan on immune and hemopoietic cell lineages in murine spleen and bone marrow.

Current evidence indicates an immunostimulating role for complex carbohydrates, i.e., polysaccharides, from several plant sources. In the present work, we determined the specific in vivo effects, with time of administration, of one such compound, a neutral arabinogalactan from larch not only on immune (lymphoid) cells, but also on natural killer (NK) lymphoid cells, as well as a variety of other hemopoietic cells in both the bone marrow and spleen of healthy, young adult mice. The latter were injected daily (i.p.) with arabinogalactan (500 microg in 0.1 ml pH 7.2 phosphate buffered saline-PBS) for 7 or 14 days. Additional, aged (1 1/2-2 yr) mice were similarly injected for 14 days only. Control mice were given the PBS vehicle in all cases, following the above injection regimen. Animals from all groups were sampled 24 h after the final injection and the immune and hemopoietic cell populations in the bone marow and spleen were assessed quantitatively. The results indicated that immediately following either 7 or 14 days of arabinogalactan administration to young, adult mice, lymphoid cells in the bone marrow were significantly decreased (p < 0.004; p < 0.001, respectively) relative to controls but remained unchanged at both time intervals in the spleen. NK cells, after 7 days of arabinogalactan exposure, were also decreased significantly in the bone marrow (p < 0.02), but unchanged in the spleen. After 14 days' exposure to the polysaccharide, NK cells in the bone marrow had returned to normal (control) levels, but were increased in the spleen (p < 0.004) to levels greater than 2-fold that of control. Among other hemopoietic cell lineages, none was influenced in the bone marrow or spleen by one-week administration of arabinogalactan; however, after two-week exposure, precursor myeloid cells and their mature (functional) progeny (granulocytes), were significantly reduced in the spleen (p < 0.043; p < 0.006, respectively), as were splenic monocytes (p < 0.001). These lineages in the bone marrow, however, remained steadfastly unaltered even after 14 days of continuous exposure to the agent. Of the vast cascade of cytokines induced in the presence of this polysaccharide, it appears that immunopoiesis- and hemopoiesis-inhibiting ones are most prevalent during at least the first two weeks of daily exposure.

Animals↗
PubMed1967

Hemopoietic spleen colony studies. II. Erythropoiesis.

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice. 1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells. 2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously. 3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development. 4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis. Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies. On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.

Animals↗
PubMed1972

Genetic control of thymus-derived cell function. I. In vitro DNA synthetic response of normal mouse spleen cells stimulated by the mitogens concanavalin A and phytohemagglutinin.

Concanavalin A- or phytohemagglutinin-stimulated DNA synthetic responses of 1 million normal mouse spleen cells in vitro were significantly different among various inbred strains. BALB/cJ (H-2(d)) responded better than C57BL/6J (H-2(b)) spleen cells, and the responses of C3H/HeJ or AKR/J (both H-2(k)) cells were intermediate. These responses, measured as the increment in thymidine-(3)H incorporation of mitogen-stimulated compared with unstimulated cultures, varied according to the number of cells cultured or the mitogen concentration. BALB/c spleens had the highest proportion of theta-positive cells, but no direct relationship between the proportion of theta-positive cells and the DNA synthetic response was observed. (BALB/cJ x C57BL/6)F(1) spleen cells responsed as well as BALB/c cells. Responses of spleen cells from (F(1) x C57BL/6) backcross littermates varied over a range equal to, or greater than, that of BALB/c and C57BL/6 cells. There was no correlation between H-2 specificity (H-2(bd) or H-2(bb)) or sex and the mitogen-stimulated DNA synthetic response of backcross animals. Con A- and PHA-stimulated responses of individual backcross animals were positively correlated with the level of thymidine-(8)H incorporation by unstimulated spleen cells. These results are consistent with autosomal dominant, non-H-2-linked, polygenic control of the mitogen-stimulated in vitro DNA synthetic response of mouse spleen cells.

Animals↗
PubMed1973

Genetic control of immune responses in vitro. II. Cellular requirements for the development of primary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro.

The cellular requirements for the development of primary IgG GAT-specific PFC responses in cultures of spleen cells from responder, C57Bl/6, mice stimulated with GAT and GAT-MBSA and in cultures of spleen cells from nonresponder, SJL and B10.S, mice stimulated with GAT-MBSA were investigated. Macrophages were required for development of responses to GAT and GAT-MBSA in cultures of spleen cells from responder mice and for responses to GAT-MBSA in cultures of spleen cells from nonresponder mice. Macrophages from nonresponder mice supported the development of responses to GAT by nonadherent responder spleen cells, indicating that the failure of nonresponder mice to respond to GAT is not due to a macrophage defect. Furthermore, responder macrophages supported the responses of nonadherent, nonresponder spleen cells to SRBC and GAT-MBSA, but not to GAT. This indicates that the capacity to respond to GAT is a function of the nonadherent population which is composed of thymus-derived (T) helper cells and precursors of antibody-producing cells. Treatment of spleen cells with anti-theta serum and complement before culture initiation abolished PFC responses to GAT and GAT-MBSA thus establishing the requirement for T cells in the development of PFC responses to these antigens. Since precursors of antibody-producing cells in nonresponder mice are capable of synthesizing antibody specific for GAT after stimulation with GAT-MBSA and since the response to GAT is thymus-dependent, it appears that nonresponder mice lack GAT-specific helper T cell function.

Alanine↗
PubMed1976

Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice.

The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recpients by determining: (a) the number of stem cells colonizing the spleen, (b) the rate of incorporation of 125I-labeled iododeoxyuridine by proliferating colony cells, and (c) the number of cells present in the largest colonies at the end of the growth phase.We found that the growth capacity of stem cells declined with age. We further found that the spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. On the other hand, the spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. These results suggest that the growth capacity of old stem cells is an intrinsic characteristic which cannot be readily altered, but that of young stem cells can be aged in an accelerated manner by allowing them to self-replicate in old recipients. An additional reduction was noted in the frequency of both young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. These results indicate that factors extrinsic to the stem cells are also responsible for the decline with age in their spleen colony growth capacity.Thus, the growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.

Aging↗
PubMed2003

Porcine reproductive and respiratory syndrome virus persistence in blood, spleen, lymph nodes, and tonsils of experimentally infected pigs depends on the level of CD8high T cells.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces a persistent viral infection suggesting an inefficient cellular immune response. The aim of the study was to evaluate the relationship between viral persistence and cytotoxic cells in blood, spleen, mediastinal lymph nodes (MLN) and tonsils of PRRSV experimentally infected pigs. Groups of four to six specific pathogen-free (SPF) pigs were infected with the LHVA-93-3 isolate, and blood and lymphoid organs were collected from 3 to 60 days post-infection (p.i.). Infectious particles and viral RNA were more or less rapidly eliminated in serum, spleen, lungs and MLN but persisted the longest in tonsils. Lymphocytes CD2+ CD4+, CD2+ CD8high, CD2+ CD8low and NK cells populations were phenotyped and their reactivity to PHA and ConA were tested. Analysis of T cell subsets in blood and lymphoid organs indicated that the percentages of CD2+ CD8+ T cells slightly increased in spleen at 17 days p.i, whereas no changes were observed in CD2+ CD4+ cells in blood or lymphoid organs. However, discrimination of CD8+ cells in CD8high and CD8low subsets revealed that the percentages of CD2+ CD8high cells increased in spleen and blood from 10 to 45 or 60 days p.i. while they transiently increased in MLN and decreased in tonsils. The CD8low/CD8high ratio increased in the blood of PRRSV-infected animals at three days p.i. due to a transient decrease of CD2+ CD8high cells. This same ratio decreased in the spleen of infected pigs from 10 to 45 days p.i. due to an increase of CD2+ CD8high cells. The CD2+ MIL-4+ cell subset (NK cells) was not significantly modified in blood or lymphoid organs. In addition, the ability of lymphoid T cells from blood and lymphoid organs to respond to ConA or PHA stimulation was transiently impaired in blood and spleen during the PRRSV persistent infection. Taken together, these results suggest that, in persistently infected pigs, an impaired CD2+ CD8high cell response in MLN and tonsils favors viral persistence in these organs, in contrast with the response seen in blood and spleen where viral elimination appears to occur sooner.

Animals↗
PubMed1998

Low CD83, but normal MHC class II and costimulatory molecule expression, on spleen dendritic cells from HIV+ patients.

Dendritic cells (DCs), which are the most potent antigen-presenting cells for T lymphocytes, are targets for HIV in vitro and in vivo. Antigen presentation by DCs has been suggested to be impaired during HIV infection; however, the extent to which DCs from HIV+ individuals are altered, particularly in lymphoid organs where T cell stimulation takes place, is not clear. To address this question, the levels of expression of functionally important molecules by spleen DCs from HIV+ patients (n = 6), and HIV- organ donors (n = 5) were compared. By rare event analysis of flow cytometry data, spleen DCs from HIV+ patients were not depleted, representing 0.6 +/- 0.4% of spleen mononuclear cells compared with 0.8 +/- 0.5% in HIV- spleens. Fresh HIV+ spleen DCs were MHC II+ and weakly CD86+CD40+, but negative for CD83 and CD80, and hence had a normal phenotype, showing no signs of in vivo activation. After 24 hr of culture, they upregulated the expression of MHC II, CD40, CD80, and CD86 to levels just as high as those on DCs from organ transplant donors. However, cultured DCs from HIV+ spleens showed lower expression of CD83, compared with DCs from HIV- spleens. The biological significance of this observation will be appreciated further when the function of this molecule is better known. These results suggest that putative defects in antigen presentation by DCs from HIV+ patients are not related to the surface expression of MHC II, CD40, CD80, or CD86.

Antigens, CD↗