International Immunology, Vol. 11, No. 7, 1065-1073,
July 1999
© 1999 Japanese Society for Immunology
Collagen-induced arthritis development requires
ß T cells but not 
T cells: studies with T cell-deficient (TCR mutant) mice
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
loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1 strains. The TCRß/ mice lacked
ß T cells, which was compensated by an expansion of B cells, 
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
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
ß T cell-independent IgM antibodies. The TCR
/ mice lacked 
T cells but had no other significant changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-
) in
/ 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 
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
ß T cells are necessary for CIA development and for an IgG response towards CII, whereas 
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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