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Intravenous tolerization with type II collagen induces interleukin‐4‐and interleukin‐10‐producing CD4 + T cells
Author(s) -
Marina L. Gumanovskaya,
Linda K. Myers,
Edward F. Rosloniec,
J. Stuart,
Andrew H. Kang
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00778.x
Subject(s) - interleukin , interleukin 2 , interleukin 1β , interleukin 4 , immunology , interleukin 3 , medicine , chemistry , microbiology and biotechnology , biology , cytokine , t cell , interleukin 21 , immune system
Intravenous (i.v.) administration of type II collagen (CII) is an effective way to induce tolerance and suppress disease in the collagen‐induced arthritis (CIA) model. In this study, we demonstrated that a single i.v. dose of CII (as low as 0·1 mg/mouse) completely prevented the development of CIA. This suppression was accompanied by decreases in levels of antibody specific for the immunogen, bovine CII and autoantigen, mouse CII. Splenocytes obtained from CII‐tolerized mice and stimulated with CII in vitro produced predominantly the T helper 2 (Th2)‐type cytokines interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10). In contrast, cells obtained from mice immunized with CII produced predominantly interferon‐γ (IFN‐γ). Two‐colour flow cytometric analysis of cytokine expression and T‐cell phenotype demonstrated that CD4 + cells and not CD8 + or γδ + cells were the predominant regulatory cells producing IL‐4 and IL‐10. Transgenic mice bearing a T‐cell receptor (TCR) specific for CII had a greater increase in the number of IL‐4‐secreting CD4 + cells, as well as a marked increase of IL‐4 in culture supernatants. This cytokine was produced by transgene‐bearing T cells. Elucidation of mechanisms for the induction of tolerance in mature T cells is an important line of study in autoimmune models because of the potential application for treating organ‐specific autoimmune disease.