The pattern of cytokine gene expression induced in rat T cells specific for myelin basic protein depends on the type and quality of antigenic stimulus.
Rat T cells reactive against myelin basic protein (MBP) are exclusively, CD4+ CD8- CD45RC-, inevitably produce abundant IFN-gamma, and appear to correspond to members of the Th1 CD4+ T cell subset characterized in mice. To ascertain the basis of the pathogenic activity of these cells, we studied their pattern of cytokine expression in response to activation by distinct TCR ligands. Using RT-PCR and Northern blot assays to quantify cytokine gene production and cytokine production from intact cells, we show that (i) rat MBP-reactive T cells express IL-2, IFN-gamma, and TNF-alpha as well as IL-5 and IL-10; (ii) cytokine production is not an all or nothing phenomenon, but rather varies according to the type and dose of TCR ligand, leading to variation in the pattern of cytokine production, or dissociation between cytokine production and cell proliferation; and (iii) nonencephalitogenic T cells do not differ appreciably from their encephalitogenic counterparts in ability to produce major cytokines.
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Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-0318, USA.
Hu
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XZ
Shah
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Coleclough
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D000939:Epitopes; D007376:Interleukin-2; D015848:Interleukin-5; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma