Podd B S, Aberg C, Kudla K L, Keene L, Tobias E, Camerini V
Department of Pediatrics and Beirne B. Carter Center for Immunology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
J Immunol. 2001 Sep 1;167(5):2561-8. doi: 10.4049/jimmunol.167.5.2561.
The development of TCR alphabeta(+), CD8alphabeta(+) intestinal intraepithelial lymphocytes (IEL) is dependent on MHC class I molecules expressed in the thymus, while some CD8alphaalpha(+) IEL may arise independently of MHC class I. We examined the influence of MHC I allele dosage on the development CD8(+) T cells in RAG 2(-/-) mice expressing the H-2D(b)-restricted transgenic TCR specific for the male, Smcy-derived H-Y Ag (H-Y TCR). IEL in male mice heterozygous for the restricting (H-2D(b)) and nonrestricting (H-2D(d)) MHC class I alleles (MHC F(1)) were composed of a mixture of CD8alphabeta(+) and CD8alphaalpha(+) T cells, while T cells in the spleen were mostly CD8alphabeta(+). This was unlike IEL in male mice homozygous for H-2D(b), which had predominantly CD8alphaalpha(+) IEL and few mostly CD8(-) T cells in the spleen. Our results demonstrate that deletion of CD8alphabeta(+) cells in H-Y TCR male mice is dependent on two copies of H-2D(b), whereas the generation of CD8alphaalpha(+) IEL requires only one copy. The existence of CD8alphabeta(+) and CD8alphaalpha(+) IEL in MHC F(1) mice suggests that their generation is not mutually exclusive in cells with identical TCR. Furthermore, our data imply that the level of the restricting MHC class I allele determines a threshold for conventional CD8alphabeta(+) T cell selection in the thymus of H-Y TCR-transgenic mice, whereas the development of CD8alphaalpha(+) IEL is dependent on, but less sensitive to, this MHC class I allele.
TCRαβ(+)、CD8αβ(+)肠道上皮内淋巴细胞（IEL）的发育依赖于胸腺中表达的MHC I类分子，而一些CD8αα(+) IEL可能独立于MHC I类产生。我们研究了MHC I等位基因剂量对表达针对雄性Smcy衍生的H-Y抗原（H-Y TCR）的H-2D(b)限制性转基因TCR的RAG 2(-/-)小鼠中CD8(+) T细胞发育的影响。对于限制性（H-2D(b)）和非限制性（H-2D(d)）MHC I类等位基因（MHC F(1)）杂合的雄性小鼠中的IEL由CD8αβ(+)和CD8αα(+) T细胞混合组成，而脾脏中的T细胞大多为CD8αβ(+)。这与H-2D(b)纯合的雄性小鼠中的IEL不同，后者主要是CD8αα(+) IEL，脾脏中几乎没有CD8(-) T细胞。我们的结果表明，H-Y TCR雄性小鼠中CD8αβ(+)细胞的缺失依赖于两个拷贝的H-2D(b)，而CD8αα(+) IEL的产生仅需要一个拷贝。MHC F(1)小鼠中CD8αβ(+)和CD8αα(+) IEL的存在表明它们的产生在具有相同TCR的细胞中并非相互排斥。此外，我们的数据表明，限制性MHC I类等位基因的水平决定了H-Y TCR转基因小鼠胸腺中常规CD8αβ(+) T细胞选择的阈值，而CD8αα(+) IEL的发育依赖于该MHC I类等位基因，但对其敏感性较低。
