Administration of recombinant human IL-1 by Staphylococcus enterotoxin B prevents tolerance induction in vivo.
Peripheral tolerance is important to prevent autoimmunity of T cells against tissue-specific autoantigens in peripheral organs. In certain pathologic situations, peripheral tolerance breaks for unknown reasons and autoimmune diseases occur. Anergy is one of the mechanisms of peripheral tolerance that down-modulates IL-2 synthesis and IL-4 responsiveness by helper T cell clones. In this report, we utilized a model system in which V beta 8+ CD4 T cells were anergized by administration of high doses of Staphylococcus enterotoxin B (SEB) in vivo and investigated an effect of recombinant human (rh) IL-1 on the tolerance induction. RhIL-1 was used because of its ability to induce IL-4 responsiveness in T cells. When rhIL-1 was administered within 24 h after SEB inoculation, the cytokine interfered with tolerance induction; V beta 8+CD4 T cells from mice that had been treated with both SEB and IL-1 proliferated in response to SEB and produced IL-2, IL-4, and IFN-gamma upon TCR/CD28 cross-linking. Delayed administration of rhIL-1 by 48 h failed to do this; T cells did not proliferate in response to SEB, but they retained an ability to produce IL-4 upon TCR/CD28 cross-linking. Administration of rhIL-1 induced better proliferation of V beta 8+CD4 T cells in response to SEB in vivo but did not prevent cell death after proliferation. These results suggest a potential role of inflammatory cytokine IL-1 in the course of autoimmunity via interference with tolerance.
Nakata
Y
Y
Division of Clinical Research and Radiation Health, National Institute of Radiologic Sciences, Chiba, Japan.
Matsuda
K
K
Uzawa
A
A
Nomura
M
M
Akashi
M
M
Suzuki
G
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology* / Q000494:pharmacology
D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D011994:Recombinant Proteins; D018089:Superantigens; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal