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。