Sydora B C, Brossay L, Hagenbaugh A, Kronenberg M, Cheroutre H
Department of Microbiology and Immunology and the Molecular Biology Institute, University of California at Los Angeles, CA 90095, USA.
J Immunol. 1996 Jun 1;156(11):4209-16.
Intestinal intraepithelial lymphocytes (IEL) are mostly CD8 single positive T cells. IEL with a TCR-alpha(beta) that are CD8 single positive are absent from beta(2)-microglobulin (beta(2)m)-deficient mice, consistent with the idea that these IEL, like other TCR-alpha(beta)+, CD8+ T cells, require class I molecules for positive selection. In contrast, here we show that substantial numbers of TCR-alpha(beta)+, CD8 single positive IEL are present in mice deficient for the transporter associated with Ag processing 1 (TAP 1) gene, although T cells with this phenotype are absent from thymus, spleen, and lymph nodes of these same mice. The majority of TCR-alpha(beta)+, CD8 single positive IEL in TAP-deficient mice expresses CD8 molecules composed of alpha(alpha) homodimers and they express a diverse set of V(beta) gene segments. In addition, the number of TCR-alpha(beta)+, CD4/CD8 double positive IEL is decreased in beta(2)m-deficient mice but not in TAP-deficient mice. The dependence of the two TCR-alpha(beta)+ IEL populations that express CD8alpha(alpha) homodimers on beta(2)m as opposed to TAP molecules is striking. It suggests that TAP-independent but beta(2)m-requiring nonclassical class I molecules expressed by cells in the intestine, such as the thymus leukemia Ag and CD1, could play a pivotal role in the development and/or the accumulation of major subpopulations of TCR-alpha(beta)+ IEL.
肠道上皮内淋巴细胞（IEL）大多为CD8单阳性T细胞。β2-微球蛋白（β2m）缺陷小鼠缺乏带有TCR-α（β）的CD8单阳性IEL，这与以下观点一致：这些IEL与其他TCR-α（β）+、CD8+ T细胞一样，需要I类分子进行阳性选择。相比之下，我们在此表明，在与抗原加工相关的转运体1（TAP 1）基因缺陷的小鼠中存在大量TCR-α（β）+、CD8单阳性IEL，尽管这些小鼠的胸腺、脾脏和淋巴结中不存在具有这种表型的T细胞。TAP缺陷小鼠中大多数TCR-α（β）+、CD8单阳性IEL表达由α（α）同二聚体组成的CD8分子，并且它们表达多种V（β）基因片段。此外，β2m缺陷小鼠中TCR-α（β）+、CD4/CD8双阳性IEL的数量减少，但TAP缺陷小鼠中未减少。表达CD8α（α）同二聚体的两个TCR-α（β）+ IEL群体对β2m而非TAP分子的依赖性很显著。这表明肠道细胞表达的不依赖TAP但需要β2m的非经典I类分子，如胸腺白血病抗原和CD1，可能在TCR-α（β）+ IEL主要亚群的发育和/或积累中起关键作用。
