Intravenous tolerization with type II collagen induces interleukin-4-and interleukin-10-producing CD4+ T cells.
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-gamma (IFN-gamma). Two-colour flow cytometric analysis of cytokine expression and T-cell phenotype demonstrated that CD4+ cells and not CD8+ or gammadelta+ 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.
Gumanovskaya
M L
ML
Departments of Internal Medicine; The Research Service of the Veterans Administration Medical Center, Memphis, TN 38163, USA.
Myers
L K
LK
Rosloniec
E F
EF
Stuart
J M
JM
Kang
A H
AH
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D003094:Collagen / Q000276:immunology*; D007108:Immune Tolerance; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013154:Spleen / Q000276:immunology
D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen