International Immunology, Vol. 11, No. 7, pp. 1065–1073
© 1999 The Japanese Society for Immunology
Collagen-induced arthritis development
requires αβ T cells but not γδ 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,
SoĢlvegatan 19, 221 00 Lund, Sweden
Keywords: autoimmunity, IgM/IgG antibodies, in vivo animal models, rheumatoid arthritis, T lymphocytes,
transgenic/knockout
Abstract
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 β or δ loci into two mouse strains susceptible to CIA, the B10.Q and DBA/1
strains. The TCRβ–/– mice lacked αβ T cells, which was compensated by an expansion of B cells, γδ
T cells and NK cells. The β–/– mice, but not control βF/– littermates, were completely resistant to
CIA. The production of anti-CII IgG antibodies was also abolished in β–/– mice, revealing a strict αβ
T cell dependency. In contrast, β–/– mice produced reduced, but significant, anti-CII IgM titers after
immunization with either CII or ovalbumin, indicating a multispecificity for these αβ T cell-
independent IgM antibodies. The TCRδ–/– mice lacked γδ T cells but had no other significant
changes in lymphocyte or monocyte subsets. The cytokine response (IL-2, IL-4, IL-10 and IFN-γ) in
δ–/– 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 γδ 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
αβ T cells are necessary for CIA development and for an IgG response towards CII, whereas γδ T
cells are neither