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International Immunology, Vol. 11, No. 7, 1065-1073, July 1999
© 1999 Japanese Society for Immunology

Collagen-induced arthritis development requires {alpha}ß T cells but not {gamma}{delta} T cells: studies with T cell-deficient (TCR mutant) mice

Alexandre Corthay, Åsa Johansson, Mikael Vestberg and Rikard Holmdahl

Department of Cell and Molecular Biology, Section for Medical Inflammation Research, Lund University, Sölvegatan 19, 221 00 Lund, Sweden

Correspondence to: A. Corthay

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 ß or {delta} loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCRß–/– mice lacked {alpha}ß T cells, which was compensated by an expansion of B cells, {gamma}{delta} T cells and NK cells. The ß–/– mice, but not control ß+/– littermates, were completely resistant to CIA. The production of anti-CII IgG antibodies was also abolished in ß–/– mice, revealing a strict {alpha}ß T cell dependency. In contrast, ß–/– mice produced reduced, but significant, anti-CII IgM titers after immunization with either CII or ovalbumin, indicating a multispecificity for these {alpha}ß T cell-independent IgM antibodies. The TCR{delta}–/– mice lacked {gamma}{delta} 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 {gamma}{delta} 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 {alpha}ß T cells are necessary for CIA development and for an IgG response towards CII, whereas {gamma}{delta} T cells are neither necessary nor sufficient for development of CIA.

Keywords: autoimmunity, IgM/IgG antibodies, in vivo animal models, rheumatoid arthritis, T lymphocytes, transgenic/knockout

Transmitting editor: M. Feldmann


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