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)

The in vivo relevance of functional dichotomy of CD4+ Th clones was studied by analyzing the induction of mRNA encoding for Th1- (IL-2) and Th2- (IL-4) specific lymphokines in a model of accelerated (24 h) cardiac allograft (Tx) rejection in presensitized rats. The polymerase chain reaction-assisted screening of total cellular RNA from cardiac Tx of otherwise untreated sensitized recipients has revealed sequential lymphokine mRNA expression, with the peak of IL-2 mRNA (6-12 h) preceding that for IL-4 mRNA, which was maximal at the time of actual Tx loss (24 h). Both IL-2 and IL-4 transcripts could be readily detected by polymerase chain reaction analysis in the spleens during the course of accelerated rejection. Treatment of prospective cardiac Tx recipients with BWH-4, a mouse anti-rat CD4 mAb, abrogated rejection at 24 h and prolonged cardiac Tx survival to ca. 11 days, coinciding with significantly diminished IL-2 mRNA expression. In contrast, CD4 targeted therapy preserved intra-Tx and splenic transcription of the IL-4 gene. Spleen lymphocytes from mAb-conditioned recipients separated by magnetic microspheres into phenotypically distinct subpopulations, showed differential induction of IL-2 and IL-4 mRNA. Thus, IL-2 mRNA was at most very weakly expressed, whereas IL-4 transcription was strongly induced both in CD4+ T cells and its OX-22- subset. This study demonstrates the induction of IL-4 mRNA in situ in the rat system, describes discordant elaboration of IL-2 and IL-4 mRNA in untreated/anti-CD4 mAb-treated cardiac Tx recipients, and identifies OX-22- CD4+ T cells as the IL-4 mRNA producers. Thus, these results provide evidence for functional heterogeneity of rat CD4+ T cells in vivo, as defined by divergent mRNA lymphokine transcription profiles.
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PMID:Evidence for functional heterogeneity of rat CD4+ T cells in vivo. Differential expression of IL-2 and IL-4 mRNA in recipients of cardiac allografts. 134 48

Immunization of naive or specifically primed C3H/HEJ with irradiated B10.BR spleen cells via the hepatic portal vein leads to an antigen specific decrease in the proliferative and cytotoxic response to B10.BR antigen assayed in vitro (and to increased graft survival of B10.BR grafts in vivo). This effect seems to be mediated in the main by a decrease in IL-2 production from CD4+ T lymphocytes of mice given antigen by the portal route, which is in turn caused by a decreased precursor frequency of IL-2-producing cells. No clear decrease in IL-4 production was seen. Hepatic APC isolated from mice receiving antigen via the portal vein were unable to induce IL-2 production from a C3H/HEJ anti-B10.BR cell line in vitro, in contrast to splenic APC derived from the same mice. Even when antigen was given by conventional (systemic) intravenous routes (in this case via the lateral tail vein) hepatic APC isolated from those mice were unable to stimulate IL-2 production from this cell line. Furthermore, 24 h exposure of a cell line to antigen pulsed hepatic APC left those cells refractory to a subsequent restimulation with antigen presented by splenic APC. Spleen lymphoid cells from primed mice challenged in vivo with B10.BR liver cells (i.v.) were similarly unable to produce IL-2 on rechallenge in vitro with irradiated B10.BR spleen cells, though no defect was seen if in vivo challenge was with B10.BR spleen cells. These data imply that presentation of multiple minor cell surface antigens by hepatic APC leads to specific anergization of IL-2 producing T cells, in a fashion which seems to be distinct from that previously reported as due to 'veto-like' activity.
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PMID:Immunosuppression induced by hepatic portal venous immunization spares reactivity in IL-4 producing T lymphocytes. 142 92

Granulomas around Schistosoma mansoni eggs are a principal cause of morbidity in mice infected with this helminth. In vivo treatment of infected mice with anti-IL-2 antibodies, with or without anti-IL-2 receptor antibodies, significantly diminished the size of circumoval granulomas in the liver and decreased hepatic fibrosis to half that in untreated mice. Antibody-treated animals also displayed a marked reduction in both peripheral blood and tissue eosinophilia while IgE levels were unchanged or increased. Spleen cell cytokine production in response to Ag or mitogen stimulation was selectively altered by in vivo anti-IL-2 administration. IL-5 responses were dramatically reduced, whereas IL-4, IL-2, and IFN-gamma responses were not consistently changed. These findings confirm previous observations, suggesting a role for IL-2 in egg-induced pathology but indicate that the primary function of this cytokine in schistosome-infected mice may be in the generation of Th2- rather than Th1-associated responses.
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PMID:Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production. 153 55

Recent studies indicate that egg granuloma formation in murine Schistosoma mansoni infection is associated with Th2-mediated immune responses. The present study was designed to analyze dynamically the Th1 and Th2 responses in S. japonicum-infected animals and compare them with the results seen with S. mansoni. C3H mice were infected with 10 to 20 cercariae of S. japonicum and sacrificed 3 to 22 weeks later. Spleen cells were stimulated with parasite antigens (egg and adult worm) or the mitogen concanavalin A. Interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon (IFN-gamma) levels were measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA) or bioassays. Additionally, cytokine-producing cells were enumerated by ELISPOT. The results show that Th2 cytokine production, characterized by IL-4 and IL-5, represents the major response in the first month after egg laying begins, while the Th1 functions of IFN-gamma and IL-2 production are greatly depressed. However, by 22 weeks Th2 responses have diminished and IFN-gamma production in response to concanavalin A is apparent. IL-2 responses are minimal at all times. In vitro depletion of T-cell subsets indicates that CD4+ cells are the major subset responsible for production of IL-5 at 7 weeks of infection. These findings suggest that, as in the case of S. mansoni infection, S. japonicum-induced immunopathology is temporally associated with the host Th2 response, although other experiments indicate that IFN-gamma is also involved.
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PMID:Dynamic analysis of splenic Th1 and Th2 lymphocyte functions in mice infected with Schistosoma japonicum. 167 41

The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.
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PMID:Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice. 191 23

Spleen cell populations depleted of both B and T lymphocytes produce interleukin 4 (IL-4) in response to stimulation with immunoglobulins bound to the surface of culture dishes. In the presence of interleukin 3 (IL-3), plate-bound (PB) IgE and PB-IgG1, IgG2a, and IgG2b are excellent stimulants, whereas PB-IgA and PB-IgM fail to stimulate IL-4 production. In the absence of IL-3, PB-IgE stimulates relatively modest production of IL-4, whereas PB-IgG2a generally does not. The response to PB-IgE is inhibited by soluble IgE; antibody to Fc gamma receptor II inhibits the response to PB-IgG2a. Thus, separate receptors mediate these stimulations, and Fc receptor cross-linkage is required for IL-4 production. Depletion of cells expressing asialo-GM1 does not diminish IL-4 production in response to PB immunoglobulins, indicating that natural killer cells are not essential for non-B, non-T cell production of IL-4. In addition to IL-4, non-B, non-T cells produce IL-3, but no detectable interleukin 2 or interferon gamma. Non-B, non-T cells may be an important source of lymphokines in a variety of immune responses and may serve to amplify the effects of T cells of the TH2 type.
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PMID:Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines. 210 35

The gp63 gene of Leishmania major was transformed into the AroA- vaccine strain of Salmonella typhimurium (SL3261). The construct (SL3261-gp63), which stably expresses the gp63 Ag in vitro, was used to immunize CBA mice by the oral route. Spleen cells from mice inoculated with SL3261-gp63 developed antibody and proliferative T cell response to L. major. They did not express detectable delayed-type hypersensitivity reactivity. The activated T cells are mainly CD4+ and secrete IL-2 and IFN-gamma but no IL-4. The orally immunized mice developed significant resistance against a challenge L. major infection. We have, therefore, demonstrated the feasibility of oral vaccination against leishmaniasis and that the oral route of antigen delivery via the heterologous carrier may preferentially induce Th1 subsets of CD4+ cells.
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PMID:Oral Salmonella typhimurium (AroA-) vaccine expressing a major leishmanial surface protein (gp63) preferentially induces T helper 1 cells and protective immunity against leishmaniasis. 214 49

Levels of IFN-gamma, IL-2 and IL-4 were measured in vitro during the course of non-lethal Plasmodium chabaudi adami and lethal P. chabaudi strain 1309 infections in BALB/cByJ mice. Spleen cells from mice infected with the non-lethal Plasmodium had a higher initial response to P. chabaudi antigens than mice infected with P. chabaudi strain 1309, as determined by measuring all three lymphokines. We conclude that both Th1 and Th2 subsets of T helper lymphocytes are activated during P. chabaudi adami infection but that these responses are suppressed in mice infected with the more virulent P. chabaudi strain 1309.
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PMID:Cytokine production in lethal and non-lethal murine malaria. 214 59

The present study shows that interleukin 4 (IL4) can exert either stimulatory or inhibitory effects on an antigen-specific IgE response in vitro. Spleen cells from BALB/c mice that had been primed with trinitrophenyl keyhole limpet hemocyanin (TNP-KLH) were cultured with the same antigen for 2 days, washed, transferred to an antigen-free culture medium, and then cultured for 4 days. Anti-TNP IgE antibodies secreted into the medium were determined by an enzyme immunoassay developed in our laboratory. Anti-TNP IgE response was elicited by TNP-KLH in cultures of the spleen cells from mice that had been primed twice with the antigen at an interval of 3 weeks, but not in cells from animals that had received only a single injection of the antigen. When the latter cells were cultured with the antigen in the presence of mouse recombinant IL4, a considerable level of the antigen-specific IgE response was induced. In contrast, the IgE response elicited in the cells of mice that had been primed twice with the antigen was markedly down-regulated by added IL4. These observations suggest a novel function of IL4 in the regulation of IgE antibody responses.
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PMID:Effects of interleukin 4 on an antigen-specific IgE response in vitro in murine lymphocytes. 234 1

Lymphocytes of autoimmune mice have been reported to have defective IL-2 production and proliferation in response to the mitogen concanavalin A. We have examined transcription of lymphokine genes in Con A stimulated spleen cells from both autoimmune and normal mice and found that IL-2, IL-4 and gamma-interferon (IFN gamma) were induced in all mice tested. Spleen cells were taken from young (pre-disease) or old (clinically active) MRL/lpr (lpr) and male BXSB autoimmune mice and from their normal counterparts (MRL/n, BXSB females, BALB/c and DBA/2) and stimulated with Con A. Con A induced production of IL-2, IL-4 and IFN gamma message and protein, and kinetics of induction did not vary significantly among the strains. However, in old lpr mice, levels of IL-2 protein and mRNA were about 10-fold lower than in other strains; IL-4 protein and mRNA were decreased approximately three-fold; and IFN gamma mRNA was readily detected in unstimulated cells and low but detectable levels of protein were produced constitutively. In contrast, little or no defect in IL-2 or IL-4 transcription or secretion were seen in male BXSB mice and no constitutive IFN gamma transcription was seen in this strain. These data indicate that all three lymphokine genes are activated by Con A in autoimmune mice, even though Con A-induced proliferation is defective in these mice. Furthermore, autoimmune mouse strains vary in terms of lymphokine expression: male BXSB mice display a normal lymphokine profile, whereas lpr mice show a marked imbalance of lymphokines compared to normal controls.
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PMID:Expression of lymphokine genes in splenic lymphocytes of autoimmune mice. 250 45


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