Collagen-induced arthritis development requires αβ T cells but not γδ T cells:: studies with T cell-deficient (TCR mutant) mice
Collagen-induced arthritis development requires αβ T cells but not γδ T cells:: studies with T cell-deficient (TCR mutant) mice
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DOI：
10.1093/intimm/11.7.1065
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发表时间：
1999-07-01
影响因子：
4.4
通讯作者：
Holmdahl, R
中科院分区：
文献类型：
--
作者：
Corthay, A;Johansson, Å;Holmdahl, R
小鼠II型胶原（CII）诱导的关节炎（CIA）是类风湿性关节炎（RA）的模型，其中T淋巴细胞的作用仍有争议。为了阐明这一点，我们将TCR β或δ基因座的靶向基因缺失培育到对CIA易感的两种小鼠品系B10.Q和DBA/1品系中。TCR β（-/-）小鼠缺乏α β T细胞，这通过α细胞、γ δ T细胞和NK细胞的扩增来补偿。β（-/-）小鼠，但不是对照β（+/-）同窝出生的小鼠，对CIA完全耐药。在β（-/-）小鼠中也消除了抗CII IgG抗体的产生，揭示了严格的ap T细胞依赖性。相比之下，β（-/-）小鼠产生减少，但显着的，抗CII IgM滴度免疫后，无论是CII或卵清蛋白，表明这些ap T细胞非依赖性IgM抗体的多特异性。TCR δ（-/-）小鼠缺乏γ δ T细胞，但淋巴细胞或单核细胞亚群没有其他显著变化。的细胞因子应答同样地，考虑到关节炎发病率、疾病发作的天数、最大关节炎评分、抗CII IgG滴度和病程。我们的结论是，α β T细胞是必要的CIA发展和对CII的IgG反应，而γ δ T细胞既不必要也不足以发展CIA。
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 TCR beta(-/-) mice lacked alpha beta T cells, which was compensated 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 beta(-/-) mice, revealing a strict ap 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 ap 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 beta 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.