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

C57BL/6 (B6) mice with targeted mutations of immune function genes were used to investigate the mechanism of recovery from experimental autoimmune encephalomyelitis (EAE). The acute phase of passive EAE in the B6 mouse is normally resolved by partial recovery followed by mild sporadic relapses. B6 TCR beta-chain knockout (KO) recipients of a myelin oligodendrocyte glycoprotein p35-55 encephalitogenic T cell line failed to recover from the acute phase of passive EAE. In comparison with wild-type mice, active disease was more severe in beta(2)-microglobulin KO mice. Reconstitution of TCR beta-chain KO mice with wild-type spleen cells halted progression of disease and favored recovery. Spleen cells from T cell-deficient mice, IL-7R KO mice, or IFN-gamma KO mice were ineffective in this regard. Irradiation or treatment of wild-type spleen cell population with anti-NK1.1 mAb before transfer abrogated the protective effect. Removal of DX5(+) cells from wild-type spleen cells by anti-DX5 Ab-coated magnetic beads before reconstitution abrogated the suppressive properties of the spleen cells. TCR-deficient recipients of the enriched DX5(+) cell population recovered normally from passively induced acute disease. DX5(+) cells were sorted by FACS into DX5(+) alpha beta TCR(+) and DX5(+) alpha beta TCR(-) populations. Only recipients of the former recovered normally from clinical disease. These results indicate that recovery from acute EAE is an active process that requires NK1.1(+), DX5(+) alpha beta(+) TCR spleen cells and IFN-gamma.
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PMID:Regulation of experimental autoimmune encephalomyelitis in the C57BL/6J mouse by NK1.1+, DX5+, alpha beta+ T cells. 1123 73

The mechanism of gamma interferon (IFN-gamma) production induced by listeriolysin O (LLO), a cytolytic virulence factor of Listeria monocytogenes, was analyzed with special reference to the involvement of macrophage-derived cytokines in spleen cells of mice. LLO purified from the culture supernatant of L. monocytogenes was capable of inducing a high level of IFN-gamma when its cytolytic activity was blocked by cholesterol treatment. The IFN-gamma-inducing ability of LLO was not dependent on possibly contaminating lipopolysaccharide. Depletion of CD11b(+) cells resulted in a profound decrease in IFN-gamma production in response to LLO stimulation. Negative selection also suggested the contribution of DX5(+) cells in IFN-gamma production. Reverse transcription-PCR revealed that expression of interleukin-12 (IL-12) p35 and p40 was induced by LLO but that the IL-18 mRNA level in the CD11b(+) fraction of spleen cells was unchanged. There was no change in the expression of the IFN-gamma-inducing cytokine genes in the CD11b(-) fraction. Neutralization of IL-12 and IL-18 in culture abolished the IFN-gamma production almost completely. Spleen cells from IL-12- or IL-18-deficient mice never produced IFN-gamma after stimulation with LLO. These results clearly indicated that LLO, a well-known virulence factor of L. monocytogenes, is capable of inducing IFN-gamma from NK cells through induction of IL-12 and IL-18 from macrophages. LLO appeared to play essential roles, not only as a bacterial virulence factor but also as a bacterial modulin in the immune response of the host.
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PMID:Essential role of interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells. 1185 82