CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and prevention of thyroiditis
CD7 and CD28 are required for murine CD4+CD25+ regulatory T cell homeostasis and prevention of thyroiditis
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DOI：
10.4049/jimmunol.172.2.787
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Haynes, BF
中科院分区：
文献类型：
--
作者：
Sempowski, GD;Cross, SJ;Haynes, BF
CD 7和CD 28是T细胞IG超家族分子，具有共同的信号传导机制。为了确定CD 7和CD 28在外周淋巴细胞发育和功能中可能发挥的作用，我们产生了CD 7/CD 28双缺陷小鼠。CD 7和CD 28单缺陷和CD 7/CD 28双缺陷小鼠的胸腺和脾脏中CD 4和CD 8单阳性T细胞水平正常。然而，与野生型小鼠相比，CD 28缺陷小鼠脾脏中的CD 4（+）CD 25（+）T细胞减少，与野生型和CD 28缺陷小鼠相比，CD 7/CD 28双缺陷小鼠胸腺和脾脏中的CD 4（+）CD 25（+）T细胞数量减少。功能研究表明，来自CD 28缺陷和CD 7/CD 28双缺陷小鼠的CD 4（+）CD 25（+）T细胞可介导抑制CD 3 mAb激活CD 4（+）CD 25（-）野生型T细胞，但不如野生型CD 4（+）CD 25（+）调节性T细胞。老年CD 7/CD 28双缺陷小鼠（> 1岁）发生甲状腺炎，而在年龄匹配的对照小鼠或单一CD 7或CD 28缺陷小鼠中未观察到甲状腺炎，因此表明体内调节性T细胞的丢失允许自发性甲状腺炎的发生。综上所述，这些数据证明了CD 7和CD 28在确定胸腺和外周免疫部位的CD 4（+）CD 25（+）T调节细胞的数量和功能以及自发性甲状腺炎的发生中的协同作用。免疫学杂志，2004，172：787-794.
CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient mice had decreased CD4(+)CD25(+) T cells in spleen compared with wild-type mice, and CD7/CD28-double-deficient mice had decreased numbers of CD4(+)CD25(+) T cells in both thymus and spleen compared with both wild-type and CD28-deficient mice. Functional studies demonstrated that CD4(+)CD25(+) T cells from CD28-deficient and CD7/ CD28-double-deficient mice could mediate suppression of CD3 mAb activation of CD4(+)CD25(-) wild-type T cells, but were less potent than wild-type CD4(+)CD25(+) T regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice ( > 1 year) that was not seen in age-matched control mice or single CD7- or CD28-deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for the development of spontaneous thyroiditis. Taken together, these data demonstrated collaborative roles for both CD7 and CD28 in determination of number and function of CD4(+)CD25(+) T regulatory cells in the thymus and peripheral immune sites and in the development of spontaneous thyroiditis. The Journal of Immunology, 2004, 172: 787-794.