Synergistic interactions of IL-1 and IL-6 in T cell activation. Mitogen but not antigen receptor-induced proliferation of a cloned T helper cell line is enhanced by exogenous IL-6.
Recent reports have indicated that in addition to its well characterized effects on B cells and hepatocytes. IL-6 also affects murine and human T cells and thymocytes. Our study was designed to analyze the effects of IL-1 and IL-6 in providing a second signal in T cell activation in the D10.G4.1 assay. Highly purified human rIL-6 was tested. rIL-6 had modest but detectable activity in the D10.G4.1 assay. Maximal enhancement of proliferation induced by IL-6 in the presence of mitogen in the D10.G4.1 assay was always far less than that induced by IL-1. The D10.G4.1 assay was used to test the possibility of synergistic interactions between IL-1 and IL-6. Quantities of IL-6 which alone were not costimulatory to D10 cells enhanced IL-1-induced D10 proliferation significantly when Con A was used as a costimulus. This synergistic response could be partially blocked by antibodies to rIL-6 and fully blocked by a mAb to rIL-1 alpha. In contrast, when 3D3 (a clonotypic activating anti-TCR mAb) was used as a costimulus, no synergistic interaction between IL-1 and IL-6 could be detected. The proliferation of D10 cells induced by IL-1 and 3D3 was unaffected by antibodies to IL-6 but was completely neutralized by antibodies to IL-1. These data suggest that although IL-6 alone cannot substitute for IL-1 in functional assays for IL-1, the presence of IL-6 significantly enhances T cell responses to IL-1 in the context of the appropriate costimulatory signal. These observations have important implications regarding the specificity and utility of the D10.G4.1 assay for the measurement of IL-1 in biologic samples.
Mizutani
H
H
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520.
May
L T
LT
Sehgal
P B
PB
Kupper
T S
TS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000502:physiology; D002999:Clone Cells / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins