Collagen-induced arthritis development requires alpha beta T cells but not gamma delta T cells: studies with T cell-deficient (TCR mutant) mice.
Collagen type II (CII)-induced arthritis (CIA) in mice is a model for rheumatoid arthritis (RA) in which the role of T lymphocytes remains controversial. To clarify this, we have bred a targeted gene deletion of TCR beta or delta loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCRbeta-/- mice lacked alphabeta T cells, which was compensated by an expansion of B cells, gammadelta T cells and NK cells. The beta-/- mice, but not control beta+/- littermates, were completely resistant to CIA. The production of anti-CII IgG antibodies was also abolished in beta-/- mice, revealing a strict alphabeta T cell dependency. In contrast, beta-/- mice produced reduced, but significant, anti-CII IgM titers after immunization with either CII or ovalbumin, indicating a multispecificity for these alphabeta T cell-independent IgM antibodies. The TCRdelta-/- mice lacked gammadelta T cells but had no other significant changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-gamma) in delta-/- mice, quantified by flow cytometry staining of mitogen-stimulated lymphocytes, was indistinguishable from normal mice. Likewise, no statistically significant differences were observed in CIA between mice lacking gammadelta T cells and control littermates, considering arthritis incidence, day of disease onset, maximum arthritic score, anti-CII IgG titers and disease course. We conclude that alphabeta T cells are necessary for CIA development and for an IgG response towards CII, whereas gammadelta T cells are neither necessary nor sufficient for development of CIA.
Corthay
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Department of Cell and Molecular Biology, Section for Medical Inflammation Research, Lund University, Sölvegatan 19, 221 00 Lund, Sweden.
Johansson
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Vestberg
M
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Holmdahl
R
R
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D017353:Gene Deletion; D018095:Germ-Line Mutation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003094:Collagen