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

Corthay, Alexandre LU ; Johansson, Åsa LU ; Vestberg, Mikael LU and Holmdahl, Rikard LU (1999) In International Immunology 11(7). p.1065-1073
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 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... (More)
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. (Less)
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published
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in
International Immunology
volume
11
issue
7
pages
1065 - 1073
publisher
Oxford University Press
ISSN
1460-2377
DOI
10.1093/intimm/11.7.1065.
language
English
LU publication?
yes
id
d6d3a0d7-d5b3-46a5-a664-1d343b02909e
date added to LUP
2024-06-05 10:37:49
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2024-06-05 12:16:21
@article{d6d3a0d7-d5b3-46a5-a664-1d343b02909e,
  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 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.}},
  author       = {{Corthay, Alexandre and Johansson, Åsa and Vestberg, Mikael and Holmdahl, Rikard}},
  issn         = {{1460-2377}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1065--1073}},
  publisher    = {{Oxford University Press}},
  series       = {{International Immunology}},
  title        = {{Collagen-induced arthritis development requires alpha beta T cells but not gamma delta T cells: studies with T cell-deficient (TCR mutant) mice}},
  url          = {{http://dx.doi.org/10.1093/intimm/11.7.1065.}},
  doi          = {{10.1093/intimm/11.7.1065.}},
  volume       = {{11}},
  year         = {{1999}},
}