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 investigated the production of IL-2 and IFN-gamma (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice. Cytokine production was evaluated in culture supernatants by CTLL proliferation (IL-2), ELISA (IFN-gamma), CT4.S proliferation (IL-4) and in mRNA extracted from activated CD4+ cells by RT-PCR (IL-2, IFN-gamma and IL-4). Results show that the production of IL-2, as protein and mRNA, is profoundly depressed by aging, whereas that of IFN-gamma, as protein and mRNA, firstly declines and then increases with age. The production of IL-4, as protein, monotonically declines with aging whereas, as mRNA, firstly decreases and then increases above the level in young mice. Spleen cells in culture were also incubated with mitogens and with a recombinant cytokine (IL-1 beta, IL-2, IL-3, IL-4, IL-12 or IFN-gamma) at various concentrations. It was found that recombinant cytokines by and large enhance cytokine production when the level induced by mitogens only is low. This conclusion applies to IL-2 and IFN-gamma production as protein and mRNA. The addition of recombinant cytokines also increases the production of IL-4 at the protein level in spleen cells from old mice but, at the mRNA level, only in spleen cells from young mice. This finding suggests age-related changes in IL-4-specific mRNA transcription rate and post-transcriptional half-life as well as translation kinetics.
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PMID:Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. 908 80

Pneumocystis carinii is a major opportunistic pathogen and leading cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-gamma) in response to both types of antigen, indicative of a Th1 response; however, after 72h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-gamma and elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-gamma, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-gamma antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-gamma mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-gamma. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P. carinii infection in vivo.
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PMID:Cytokine responses to the native and recombinant forms of the major surface glycoprotein of Pneumocystis carinii. 927 20

To gain a better understanding of inherent gender-related effects on autoimmunity, cytokine genes were examined in female and male New Zealand Black X New Zealand White (B/W) mice, which are a murine model of systemic lupus erythematosus (SLE). In preliminary studies, semiquantitative reverse transcriptase-polymerase chain reaction analysis showed a trend for B/W spleen cell interferon gamma (IFN-gamma) mRNA in B/W female spleen cells to exceed that of males. This difference was obliterated following concanavalin A (Con A) stimulation. Spleen cells from B/W mice of both sexes were then examined at 6, 18, and 27 weeks of age, and results were compared with matched groups of nonautoimmune DBA/2 mice. Pooled splenocytes from all 12 groups of animals were compared simultaneously for expression of mRNA specific for IFN-gamma, interleukin 4 (IL-4) and interleukin 6 (IL-6). Strain was a potent influence on cytokine transcripts. In unstimulated splenocytes from female and male B/W mice, there was a notable trend for IFN-gamma and IL-6 mRNA expression to exceed transcripts from nonautoimmune DBA/2 mice. When comparisons were carried out by gender, a highly significant increase of IFN-gamma transcripts was apparent in B/W females compared to B/W males at the age of 27 weeks. Following Con A incubation, strain and gender differences were eliminated. IL-4 transcript expression was similar in all pools of cells, and age was not an important factor in expression of any transcript. This study represents the first examination of multiple cytokine transcripts in lymphoid cells from B/W mice. In this hormone-sensitive model of SLE, strain and gender determined in vivo expression of IFN-gamma and IL-6 mRNA.
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PMID:Cytokine mRNA expression in the B/W mouse model of systemic lupus erythematosus--analyses of strain, gender, and age effects. 928 84

Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndrome (HSS) while the rest present with moderate splenomegaly syndrome (MSS). HSS and MSS mice differ pathophysiologically (degree of splenomegaly, anaemia, ascites, periportal fibrosis, portal hypertension) and immunologically with regard to antibodies (idiotypic expression, isotype levels) to schistosome soluble egg antigens (SEA), and spleen cell phenotypic profiles. This study compared in vitro proliferative responses and IL-2, IFN gamma, IL-4, and IL-10 production by spleen cells from uninfected mice and mice with acute (8 wk), MSS or HSS schistosomiasis mansoni, upon exposure to anti-CD3 epsilon or SEA, Spleen cells from uninfected mice produce Il-2 to anti-CD3 epsilon but exposure of cells from all three groups of infected mice to anti-CD3 epsilon or SEA led to only very low levels of supernatant IL-2. Anti-CD3 epsilon- or SEA-stimulated production of IFN gamma or Il-4, and anti-CD3 epsilon-stimulated production of IL-10, displayed similar patterns: highest cytokine production by cells from mice with acute infections and lower levels of production that did not differ between the two chronic groups. In contrast, while SEA-stimulated IL-10 production was again highest with cells from mice with acute infections, spleen cells from mice with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a role in the immunoregulation that occurs in chronic schistosomiasis.
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PMID:IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. 929 93

Tuberculosis is a chronic infectious disease which causes major health problems globally. Acquired resistance is mediated by T lymphocytes and executed by activated macrophages. In vitro studies have emphasized the importance of macrophage activation for mycobacterial growth inhibition. In vivo, the protective host response is focused on granulomatous lesions in which Mycobacterium tuberculosis is contained. A cellular immune response of the T helper 1 (Th1) type is considered central for control of tuberculosis. Using interleukin-6 (IL-6)-deficient mice, we here demonstrate a crucial role of this pluripotent cytokine in protection against M. tuberculosis but not against Mycobacterium bovis BCG. Infection with M. tuberculosis was lethal for the IL-6-deficient mice at inocula that were still controlled by IL-6-competent mice. Spleen cells from M. tuberculosis-infected IL-6-/- mouse mutants produced elevated levels of IL-4 and reduced levels of gamma interferon compared to the control levels. Cytofluorometric analyses of spleen cells from M. tuberculosis-infected mice revealed more-profound alterations in T-cell ratios in IL-6-/- mice than in control mice. We assume that IL-6 contributes to host resistance by its proinflammatory activity and by its influence on cytokine secretion.
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PMID:Lethal tuberculosis in interleukin-6-deficient mutant mice. 935 74

The role of antigen-presenting cells (APC) in regulating the balance of T helper type 1 (Th1) and T helper type 2 (Th2) responses and cytokine production is unclear. Dendritic cells (DC), the most potent APC for naive T cell activation, were found to regulate Th1 and Th2 cytokine profiles in a manner dependent on their tissue of origin. Using whole tissues or purified cell mixtures, spleen (systemic) DC were found to induce mainly Th1 cytokines, and Peyer's patch (mucosal) DC were found to induce predominantly Th2 cytokines. Spleen DC induced high levels of interferon-gamma (IFN-gamma) or interleukin-2 (IL-2) or both, and Peyer's patch DC induced IL-4 or IL-6 or both in spleen and Peyer's patch T cells, allogeneic mixed leukocyte reactions, or antigen-specific Th0 clones. These data suggest that the tissue of origin of DC has a significant impact on subsequent T cell development.
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PMID:Dendritic cells from Peyer's patch and spleen induce different T helper cell responses. 950 61

A common problem in human vaccinology is the limited availability of efficient and non-toxic adjuvants capable of promoting mucosal responses. The potential usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as immunological adjuvant was assessed using ovalbumin (OVA) as a model antigen. Mice were immunized by intranasal route, either with soluble OVA or OVA covalently coupled to Sfbl. Immunization with OVA-Sfbl resulted in the elicitation of about 100-fold higher titers of anti-OVA serum IgG than using OVA alone. The anti-OVA IgG subclass pattern was dominated in both groups of mice by IgG1, followed by IgG2b, IgG2a, and IgG3. Immunization with OVA-Sfbl also resulted in the elicitation of OVA-specific IgA in lung washes (24% of the total IgA), which was absent in mice immunized with OVA alone. Spleen cells from OVA-Sfbl-immunized mice also gave a much stronger proliferative response to restimulation with soluble OVA in vitro. Phenotypic analysis of proliferating cells showed an enrichment in CD4+ T cells, producing a pattern of cytokines (IL-4, IL-5, IL-6 and IL-10) characteristic of Th2-type cells. In contrast to immunization with soluble OVA alone, OVA-Sfbl induced the generation of CD8+ OVA-specific cytotoxic cells. These results demonstrate that Sfbl represents a promising mucosal adjuvant able to substantially improve cellular, humoral and mucosal responses when coupled to an antigen administered by intranasal route.
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PMID:Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant for antigens delivered by mucosal route. 954 3

To study the role of IL-4 in development of granulomatous experimental autoimmune thyroiditis (EAT), IL-4 gene-disrupted mice expressing the EAT-susceptible H-2k haplotype were generated and used for EAT induction. Spleen cells from mouse thyroglobulin (MTg) and LPS-primed IL-4(+/+) and IL-4(-/-) donors could induce severe granulomatous EAT when spleen cells were activated with MTg and anti-IL-2R mAb in the presence of IL-12. Thyroid lesions had extensive follicular cell proliferation, large numbers of histiocytes, polymorphonuclear leukocytes, and multinucleated giant cells, in addition to lymphocytes and other mononuclear cells. Expression of IFN-gamma gene mRNA and production of IFN-gamma by effector spleen cells stimulated with MTg and IL-12 were similar for both IL-4(+/+) and IL-4(-/-) mice. Although IL-4 was undetectable in IL-4(-/-) mice, expression of mRNA for IL-5, IL-10, and IL-13 and production of IL-5 by both MTg-activated spleen cells and anti-CD3-activated CD4+ T cells were comparable for cells from IL-4(+/+) and IL-4(-/-) mice, indicating that the absence of IL-4 did not prevent production of other Th2 cytokines. Production of MTg-specific IgG1 was very low or undetectable in IL-4(-/-) mice. IL-4 gene mRNA and MTg-specific IgG1 could be detected in IL-4(+/+) or IL-4(-/-) recipients only when they received effector cells from IL-4(+/+) donor mice, indicating that IL-4- and IgG1-secreting cells are of donor origin. These results demonstrate that IL-4 is not essential for development of granulomatous EAT.
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PMID:Induction of granulomatous experimental autoimmune thyroiditis in IL-4 gene-disrupted mice. 955 67

Our previous work has documented that physical or psychological stress can alter interleukin (IL)-2, IL-4, and interferon (IFN)-gamma production by spleen or lymph node cells in vitro. To determine if adrenal hormones might be mediating these stress-induced changes in type 1 and type 2 cytokines and immune effector functions, we cultured spleen cells in vitro with either the synthetic glucocorticoid dexamethasone (DEX) or the putative restorative hormone dehydroepiandrosterone (DHEA). Spleen cells were obtained from either young (5-6 weeks old) or mature (7-8 months old) BALB/c mice that were either unimmunized or immunized with the T-cell-dependent antigen keyhole limpet hemocyanin (KLH). We determined that DEX suppressed production of all three cytokines examined. DHEA was not associated with any enhancement of cytokine production. These data challenge the hypothesis that glucocorticoids can differentially regulate Th1-like versus Th2-like cytokine production. Further, they suggest that in stress paradigms in which differential regulation of cytokine production and effector function has been observed, other neuroendocrine factors in addition to glucocorticoids must be relevant.
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PMID:Adrenal hormone modulation of type 1 and type 2 cytokine production by spleen cells: dexamethasone and dehydroepiandrosterone suppress interleukin-2, interleukin-4, and interferon-gamma production in vitro. 962 36

To date, there are no ideal animal models for study of natural sensitization leading to IgE- and lymphocyte-mediated hypersensitivities. We established such a model in which four BALB/c mice were each sensitized by exposure to at least 16 mosquito Aedes aegypti bites, twice a week for 4 weeks. Four non-exposed control mice were also studied. Mosquito A. aegypti head and thorax extract, saliva, and two recombinant salivary allergens (rAed a 1 and rAed a 2) were used in vitro as antigens. Intradermal tests were performed. Serum mosquito antigen-specific IgG, IgG1, IgG2a, and total IgE were measured by ELISA; specific IgE was measured by passive cutaneous anaphylaxis (PCA). IgE responses to each antigen in the saliva were analyzed using Western blotting. Spleen lymphocyte proliferation assays were performed to determine the cell-mediated hypersensitivity response. Antigen-induced IL-4 and IFN-gamma production in the spleen lymphocytes were evaluated using ELISA. After 4 weeks, all 4 mosquito-sensitized mice developed a positive immediate wheal 20 min after skin tests with mosquito antigens, and a positive delayed papule 24 h later, while control mice did not. Also, the sensitized mice had a positive PCA response, which correlated significantly with total IgE levels (r = 0.84, p<0.05), confirming the presence of antigen-specific IgE, while none of control mice had a positive response. Antigen-specific IgG1, but not IgG2a, was increased in the sensitized mice (p<0.01). Western blotting showed that 5 of the 8 antigens which elicited mouse IgE responses, including 2 major antigens, also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens also elicited human IgE responses. The mean lymphocyte proliferation response to mosquito antigens was significantly increased in the sensitized mice (p<0.05). IL-4 production was significantly increased and IFN-gamma production was decreased, further suggesting that a Th2 immune response predominates despite the development of the delayed skin reaction. This new model of natural sensitization without using an adjuvant is potentially useful for the study of other allergic disorders as well as mosquito allergy.
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PMID:A mouse model of mosquito allergy for study of antigen-specific IgE and IgG subclass responses, lymphocyte proliferation, and IL-4 and IFN-gamma production. 969 76


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