Kubo S, Hasegawa A, Hashimoto K, Shimizu C, Kubo M, Tada T, Nakayama T
Division of Immunobiology, Science University of Tokyo, Japan.
Immunology. 1997 Dec;92(4):437-46. doi: 10.1046/j.1365-2567.1997.00382.x.
Peripheral T-cell antigen receptor V beta (TCRV beta) repertoire is influenced by clonal deletion both in the thymus and periphery. Developing thymocytes expressing certain TCRV beta are deleted by endogenous superantigens presented on major histocompatibility complex (MHC) molecules in the thymus. Likewise, mature T cells bearing particular TCRV beta chains can be clonally deleted by superantigens in the periphery. The efficiency with which T cells expressing particular V beta subunits are deleted differs depending upon which coreceptor is expressed. Indeed, while deletion of V beta 11+ splenic T cells in CBA/J (Mls-1, a I-E, + MTV 9+) mice is quite efficient for CD4+ spleen T cells, it is much less efficient for CD8+ splenic T cells. If the difference in the efficiency of deletion is due solely to the coreceptor expressed, then a transgene encoding CD4 should increase the efficiency with which CD8+ cells are deleted. To address this question, we have produced CD4 transgenic (TG) mice that express physiologic levels of CD4 on all thymocytes and peripheral CD8 T cells. CD4 molecules expressed on CD8+ splenic T cells were associated with P56lck tyrosine kinase, and were functional as evidenced by their ability to facilitate class II alloreactivity. Furthermore, we found that ectopic expression of TG CD4 molecules on CD8+ cells was able to affect the efficiency of deletion in response to superantigen stimulation. In particular, deletion of TCRV beta 11+ T cells was much less efficient for CD8+ than for CD4+ T-cell subpopulations in (CBA/J x B6) F1 mice. However, expression of the CD4 transgene on CD8+ splenic T cells from these mice increased the efficiency of deletion in the CD8+ V beta 11 T cells. Interestingly, this effect was not observed in a mature CD8+ thymocyte subpopulation. The results in this report demonstrate that CD4 molecules are involved in peripheral deletion of TCRV beta 11+ T cells in (CBA/J x B6) F1 mice, and that the TCRV beta repertoire can be altered by ectopic expression of CD4 on all T-lineage cells.
外周T细胞抗原受体Vβ（TCRVβ）库在胸腺和外周均受克隆清除的影响。表达某些TCRVβ的发育中的胸腺细胞会被胸腺中主要组织相容性复合体（MHC）分子呈递的内源性超抗原所清除。同样，带有特定TCRVβ链的成熟T细胞在外周可被超抗原进行克隆清除。表达特定Vβ亚基的T细胞被清除的效率因所表达的共受体不同而有所差异。实际上，在CBA/J（Mls-1，a I-E，+ MTV 9+）小鼠中，Vβ11 +脾T细胞的清除对于CD4 +脾T细胞而言相当高效，但对于CD8 +脾T细胞则效率低得多。如果清除效率的差异仅仅是由于所表达的共受体所致，那么编码CD4的转基因应该会提高CD8 +细胞的清除效率。为了解决这个问题，我们制备了CD4转基因（TG）小鼠，其在所有胸腺细胞和外周CD8 T细胞上表达生理水平的CD4。在CD8 +脾T细胞上表达的CD4分子与P56lck酪氨酸激酶相关联，并且其能够促进II类同种异体反应性，证明其具有功能。此外，我们发现CD8 +细胞上TG CD4分子的异位表达能够影响超抗原刺激后的清除效率。特别是，在（CBA/J×B6）F1小鼠中，TCRVβ11 + T细胞的清除对于CD8 + T细胞亚群而言比对CD4 + T细胞亚群效率低得多。然而，这些小鼠的CD8 +脾T细胞上CD4转基因的表达提高了CD8 + Vβ11 T细胞的清除效率。有趣的是，在成熟的CD8 +胸腺细胞亚群中未观察到这种效应。本报告中的结果表明，CD4分子参与了（CBA/J×B6）F1小鼠中TCRVβ11 + T细胞的外周清除，并且通过在所有T系细胞上异位表达CD4可改变TCRVβ库。
