Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here an assay to measure responses of T cells to in vitro stimulation with antigens and a T cell mitogen (ConA). Spleen cells from chickens immunized with live viruses and an inactivated antigen produced macrophage activating factors (MAF) in response to in vitro stimulation with homologous antigens. The production of MAF, quantitated by the induction of NO in a retrovirus transformed macrophage cell line, HD11 (Beug et al., 1979, Cell 18, 375) was antigen-specific and correlated well with T cell proliferation. Further studies showed that production of MAF was abrogated by cyclosporin A, anti-CD4 and anti-CD8 monoclonal antibodies. These data suggested that production of MAF required T cell activation and can be used as measure of antigen and mitogen-specific T cell responses in chickens.
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PMID:Nitric oxide inducing factor as a measure of antigen and mitogen-specific T cell responses in chickens. 869 26

Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.
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PMID:Immunotherapy with natural interleukins and/or thymosin alpha 1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice. 870 47

Spleen cells from mice resistant or sensitive to mouse acquired immune deficiency syndrome (MAIDS) were examined for cytokine mRNA. In MAIDS-resistant BALB/c mice, cytokine transcripts peaked at 1 week after infection with Type 1 cytokines [interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-12], dominating over Type 2 cytokines (IL-4, IL-10). Expression of cytokines other than IL-2 later declined to levels seen in uninfected mice. In MAIDS-sensitive B6 mice, transcripts for all cytokines were increased at 1 week and, except for IL-2, increased progressively. Spontaneous production of IFN-gamma protein was associated with enhanced mRNA expression at 1 week after infection of either strain, but none was detectable in association with even higher levels of transcripts at later times after infection of B6 mice. Spleen cells from longer-term-infected B6 mice, however, produced substantial amounts of IFN-gamma following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti-TNF-alpha antibodies blocked induction of IFN-gamma by LPS. Induction of IFN-gamma by IL-12 was potentiated by TNF-alpha following stimulation of intact spleen cells and purified CD4+ or CD8+ T cells, as well as negatively selected CD4-8- cells from infected B6 mice. Further studies showed that IFN-gamma knockout mice on a B6 background developed MAIDS with a prolonged time-course, whereas BALB/c knockout mice were unchanged in their resistance to MAIDS. These studies suggest that continuing low-level expression of IFN-gamma, stimulated by IL-12 and TNF-alpha, contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease.
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PMID:Retrovirus-elicited interleukin-12 and tumour necrosis factor-alpha as inducers of interferon-gamma-mediated pathology in mouse AIDS. 877 35

To evaluate the contributions of T-lymphocyte subsets in pulmonary immunity against Rhodococcus equi, C.B-17 SCID/beige mice were adoptively transferred with splenic lymphocytes from congenic BALB/c mice previously infected with R. equi. Spleen cells were enriched for either CD4+ or CD8+ populations before inoculation, Flow cytometry showed that each enriched population contained less than 0.5% cross contamination. Groups of adoptively transferred SCID/beige mice were sacrificed 6 and 13 d after intranasal infection with R. equi. Bacterial clearance was measured in the lungs, liver and spleen. Lesion development was assessed by gross and histopathological score and the fate of transferred cells assessed by flow cytometry and by immunohistochemistry. SCID/beige mice receiving either CD4+ or CD8+ T-cells were able to clear the infection better than control mice. On d 6 post-infection, bacterial numbers were significantly lower in the lungs of CD4+ transferred mice as compared to CD8+ mice. By d 13, both groups had cleared R. equi from all organs. CD4+ cells were however identified in the lung and spleen of CD8+ recipients at d 13 making conclusions about the role of CD8+ cells in R. equi clearance impossible. By contrast, no significant increases in CD8+ lymphocytes were observed in the organs of CD4+ recipients. All mice developed suppurative bronchopneumonia but lesions were most severe in the CD4+ group. Immunohistochemistry and flow cytometry confirmed that CD4+ and CD8+ cells had migrated to the lungs of adoptively transferred mice. Serum antibody against R, equi was not detected by ELISA in the recipients. SCID/beige mice receiving CD4-CD8- cells were unable to clear R. equi. The study supports the suggestion that CD4+ cells have a central role in R. equi clearance in mice.
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PMID:Role of CD4+, CD8+ and double negative T-cells in the protection of SCID/beige mice against respiratory challenge with Rhodococcus equi. 880 81

Previous studies have shown that the African strains of HIV-1 mostly cluster with the subtypes A, C or D based on phylogenetic analysis of the ENV nucleotide sequences. In the present investigation we have examined the immunogenic potential of full length gp120 derived from the Ugandan HIV-1 subtype A isolate, AUG06c, using computer-based prediction methods and a plasmid-mediated immunization technique. Computer-assisted analysis of the amino acid residues identified 15 potential B-cell epitopes in gp120 of AUG06c. Despite marked variation in the primary sequences, these epitopes were shown to correspond well to analogous sites in gp120 derived from the subtype B reference clones, MN and IIIBBH10. The relative positions of the epitopes indicated that E9[V3], E14[C3] and E15[V5] correspond to the previously defined principal neutralizing determinant (PND) located in the V3 loop, the CD4 binding site and gp120 "immunodominant" region, respectively. Intramuscular inoculation of BALB/c mice with the ENV clones from AUG06c or from the subtype C clone, CUG045 elicited antibodies which react with the homologous but not with the heterologous PND peptide in ELISA. However, cocktail inoculation with the ENV plasmids from AUG06c and CUG045 elicited antibodies which reacted with both peptides. Antibody response to the other predicted epitopes of AUG06c was not as strong as the response to the PND peptide. The response of the mice to DNA-mediated immunization was further tested in a proliferation assay. Spleen cells derived from the immunized mice exhibited a strong proliferative response to homologous and heterologous PND peptides in [3H]thymidine incorporation assay. DNA-mediated immunization with rgp120 of AUG06c appears to elicit cellular immune response of relatively broad specificity.
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PMID:Immunogenic potential of rgp120 from African HIV-1 subtype A. 887 94

F1 hybrid New Zealand Black (NZB) x New Zealand White (NZM) (NZB/NZW) mice spontaneously develop an autoimmune disease analogous to systemic lupus erythematosus (SLE). Testosterone experts a powerful suppressive effect on this disorder in adult NZB/NZW mice. A series of experiments was designed to determine if disease would also be suppressed by exposing fetal NZB/NZW mice to increased testosterone. A model was developed in which NZB dams carrying NZB/NZW fetuses were treated with testosterone in a dose adequate to masculinize the external genitalia in female fetuses. NZB/NZW mice that were derived from testosterone-treated dams and control NZB/NZW offspring were followed in a longevity study and had serial assays to assess development of SLE. Additional experiments were carried out to measure lymphocyte subsets and responses to mitogens. Results were compared with F1 hybrid offspring of C57BL/6 dams crossed with DBA/2 males, which are not autoimmune and do not develop SLE. Spleen cells from these groups were tested for Thy 1.2, CD4, CD8, and IgM receptors, and for responses to the mitogens Concanavalin A (ConA) and lipopolysaccharide. Control male NZB/NZW fetuses had unexpectedly high serum estradiol, which decreased significantly with maternal testosterone treatment. The testosterone-exposed male NZB/NZW fetuses developed into adults that lived longer than male NZB/NZW controls. Testosterone treatment of the dam was associated with elevated terminal anti-DNA levels but did not alter markers of renal diseases in adult NZB/NZW mice of either sex. Testosterone-exposed NZB/NZW females had altered T-lymphocyte subsets and testosterone-exposed males had increased response to ConA compared to controls. In male NZB/NZW fetuses whose mothers were administered testosterone, the naturally high level of circulating estradiol observed in untreated male fetuses was decreased significantly. This decrease was associated with an increase in longevity. This unique observation has important implications for fetal exposure to endocrine disruptors in the environment.
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PMID:Effects of altered prenatal hormonal environment on expression of autoimmune disease in NZB/NZW mice. 888 4

IDEC-CE9.1 is a macaque/human chimeric IgG1 monoclonal antibody (mAb) directed against the human T-lymphocyte receptor, CD4. CE9.1 is highly specific for the human receptor and is known to cross-react only with chimpanzee CD4. Thus, limited in vivo investigations have been performed that would be expected to reflect the behavior of this mAb in humans. CE9.1 was metabolically radiolabeled using [3H]leucine, and studies of the distribution and pharmacokinetics of [3H]CE9.1 were performed in transgenic mice bearing either the hCD4 receptor in place of the mouse receptor (CD4+), or no CD4 receptor (CD4-). Single-dose studies were performed after intravenous administration of approximately 0.4 and 100 mg/kg. The disposition of CE9.1 was highly dependent on the presence and distribution of the hCD4 receptor. After a low intravenous dose to CD4+ mice, rapid loss of [3H]CE9.1 from plasma (mean residence time < 1 hr) was accompanied by accumulation of radioactivity in the spleen (a maximum of 18% of the administered dose at 2 hr). By contrast, no significant uptake of radiolabel was observed in the spleen of CD4- mice after a low intravenous dose (< 1%), and plasma radioactivity exceeded 40% of the administered dose at 24 hr. Significant accumulation of radiolabel was observed in the liver of both CD4+ and CD4- mice (maximum of 9-13%), suggesting this process was not CD4-receptor-mediated. After a high intravenous dose to CD4+ mice, the mean residence time of CE9.1 was approximately 24 hr, and dose-normalized plasma area under the concentration vs. time curve was within a factor of 2 of that observed in CD4- mice. Spleen radioactivity was < 1% after a high intravenous dose to CD4+ mice, whereas in the liver, the profile of radioactivity was similar in CD4+ mice at 0.4 and 100 mg/kg.
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PMID:Disposition of metabolically radiolabeled CE9.1--a macaque-human chimeric anti-human CD4 monoclonal antibody--in transgenic mice bearing human CD4. 888 16

The current investigation focused on lymphoid cell populations of adult male Sprague-Dawley rats fed a total enteral nutrition diet in which ethanol provided 38% of the total calories. Rats received the National Research Council (NRC) recommended daily intake of nutrients 35 days. An evaluation of lymphocyte populations from peripheral blood demonstrated a decrease in the absolute number of B cells (p < or = 0.007) and absolute numbers of CD4 T cells (p < or = 0.06) in the ethanol-treated animals. Spleen and thymus weights were significantly reduced (p = 0.0001) in the ethanol-treated rats and the CD4/CD8 ratio of splenic lymphocytes decreased in the ethanol group (p < or = 0.03). Thymus T-cell recovery from the ethanol-treated group was significantly reduced with no apparent redistribution in subset numbers with the exception of a minor, yet significant, decrease (p < or = 0.05) in the CD4/CD8 ratio. These data are the first to demonstrate that chronic alcohol intake alters lymphoid cell populations in the peripheral blood and primary organs of the immune systems in the presence of adequate nutrition.
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PMID:Flow cytometric analysis of lymphocytes from rats following chronic ethanol treatment. 888 43

To elucidate the funciton of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tl alpha 2-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla2-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg. Tla2-3-1, Tg. Tla2-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg. Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tla2-3-1 and Tg.Tla2-3-2, respectively, expressed TCR gamma delta, whereas almost all those from C3H expressed TCR alpha beta. The MLC from Tg. Tla2-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg. Tla2-3-1 had little or none. The generation of gamma delta CTL recognizing TL in Tg. Tla2-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 gamma delta CTL clones were established from Tg. Tla2-3-2, whereas none were obtained from C3H. Of the 14 gamma delta CTL clones, 8 were CD8+ and 6 were CD4-CD8- double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCR gamma delta and CD3, and also by antibodies to CD 8 alpha and CD8 beta in CD8+ clones, showing that the activity was mediated by TCR gamma delta and coreceptors. The thymic origin of these gamma delta CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 alpha beta heterodimers in CD8+ clones on their surfaces and by the usage of TCR V gamma 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla2-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of gamma delta T cells.
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PMID:Positive selection of gamma delta CTL by TL antigen expressed in the thymus. 897 73

Autoimmune-prone MRL/lpr mice, homozygous for the lpr mutation, exhibit defective apoptosis and develop generalized lymphoproliferation with the accumulation of a double-negative (DN: CD4- CD8-) T cell population. The capacity of lpr T lymphocytes to effectuate Fas- and perforin-mediated cytotoxicity was investigated. Spleen and lymph nodes cells spontaneously lyse Fas- targets (thymocytes) through a Fas-mediated mechanism as a consequence of their overexpression of Fas ligand (FasL) confirmed by semiquantitative reverse transcription (RT)-PCR and immunoprecipitation analysis. This cytotoxicity was greatly increased after stimulation of the effectors by phorbol myristate acetate (PMA) + ionomycin. Under these conditions, MRL/lpr spleen and LN cells exhibited strong Fas-mediated Ca2+-independent cytotoxic activity against wild-type Fas+ (H-2 compatible or incompatible) thymocytes or lipopolysaccharide (LPS)-transformed blast cells. Such Fas-mediated cytotoxic activity was also observed with C57BL/6-lpr, but never with wild-type C57BL/6 or MLR+/+ effectors. Depletion experiments showed that the effector cells of this Fas-mediated cytotoxicity were DN T cells. This subset, which represent in vivo activated T cells, can spontaneously lyse Fas+ targets by a mechanism that does not need the interaction of the T cell receptor (TCR) with major histocompatibility complex molecule plus antigen. This lytic potential is increased by PMA + ionomycin, which sends a second activation signal to these primed T cells. Therefore, the small amounts of Fas receptor expressed on MRL/lpr tissues may account for their nonspecific autoimmune attack by DN cells. In Con A-containing medium, which allows detection of the perforin-mediated pathway against Fas targets, cytotoxic CD8+ effectors were detected that are able to kill lpr thymocytes via a Ca2+-dependent pathway. Thus, in MRL/lpr mice, these CD8+ cells could constitute potent cytotoxic effectors against cells presenting antigen to their TCR.
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PMID:MRL/lpr CD4- CD8- and CD8+ T cells, respectively, mediate Fas-dependent and perforin cytotoxic pathways. 904 12


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