Collagen-induced arthritis development requires alpha beta T cells but notgamma delta T cells: studies with T cell-deficient (TCR mutant) mice

Collagen type II (CII)-induced arthritis (CIA) in mice is a model for rheum atoid arthritis (RA) in which the role of T lymphocytes remains controversi al. To clarify this, we have bred a targeted gene deletion of TCR beta or d elta loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 st rains. The TCR beta(-/-) mice lacked alpha beta T cells, which was compensa ted by an expansion of a cells, gamma delta 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 be ta(-/-) mice, revealing a strict ap T cell dependency. In contrast, beta(-/ -) mice produced reduced, but significant, anti-CII IgM titers after immuni zation with either CII or ovalbumin, indicating a multispecificity for thes e ap T cell-independent IgM antibodies. The TCR delta(-/-) mice lacked gamm a delta T cells but had no other significant changes in lymphocyte or monoc yte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-gamma) in del ta(-/-) mice, quantified by flow cytometry staining of mitogen-stimulated l ymphocytes, was indistinguishable from normal mice, Likewise, no statistica lly significant differences were observed in CIA between mice lacking gamma delta T cells and control littermates, considering arthritis incidence, da y of disease onset, maximum arthritic score, anti-CII IgG titers and diseas e course. We conclude that alpha beta T cells are necessary for CIA develop ment and for an IgG response towards CII, whereas gamma delta T cells are n either necessary nor sufficient for development of CIA.