title: Anti-IL-6 receptor antibody suppressed T cell activation by inhibiting IL-2 production and inducing regulatory T cells.
abstract: T cell activation is crucial to the pathogenesis and progression of rheumatoid arthritis. Tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-6 inhibitors show marked efficacy in rheumatoid arthritis patients, but their impacts on T cell activation have remained unclear. To shed light on these impacts, we examined the effects of an anti-IL-6 receptor antibody and an anti-TNFalpha antibody on T cell activation in two experimental systems: spleen cells stimulated by anti-CD3 antibody, and purified splenic CD4 T cells stimulated by both anti-CD3 and anti-CD28 antibodies. Anti-IL-6 receptor antibody significantly (but only partially) suppressed T cell activation (as indicated by [3H]-thymidine uptake and CD25 expression) and IL-2 production in both systems, and increased the frequency of regulatory T cells among spleen cells. Anti-TNFalpha antibody had no effects in either system. Neither antibody increased the expression of markers of apoptosis in CD4 T cells. In conclusion, our results show that anti-IL-6 receptor antibody significantly (but only partially) suppressed the T cell receptor signalling-induced activation of CD4 T cells and also suggest that it achieved this partial suppression by the partial inhibition of IL-2 production and the induction of regulatory T cells. In stark contrast, anti-TNFalpha antibody had no impact on T cell activation. Extrapolating these results to the clinical treatment of rheumatoid arthritis, they suggest that IL-6 blockade inhibits T cell activation, whereas TNFalpha blockade does not.
authors.affiliation: Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Yoshida
authors.forename: Misato
authors.initials: M
authors.lastname: Hashizume
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
mesh_terms: D000818:Animals; D000906:Antibodies / Q000502:physiology*; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006131:Growth Inhibitors / Q000502:physiology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000906:Antibodies; D006131:Growth Inhibitors; D007376:Interleukin-2; D019947:Receptors, Interleukin-6