Chen F L, Kung J T
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Republic of China.
J Immunol. 1996 Mar 15;156(6):2036-44.
A comparative study of immune function and marker expression of CD4+ T cells from MHC class 1-restricted 2C TCR-transgenic (2C+) and control transgene-negative littermate (2C-) mice was performed. While 2C+CD4+ T cells resembled memory T cells on the basis of CD44highCD45RBlow expression, the majority of 2C-CD4+ T cells were of the CD44lowCD45RBhigh naive phenotype. Slightly lower levels of TCR-beta and CD3 were found on 2C+CD4+ T cell than 2C-CD4+ T cells. Vigorous proliferation by 2C-CD4+ T cells was observed upon stimulation with 1) anti-CD3 mAb presented through the FcR of macrophages; 2) immobilized (plate-bound) anti-CD3 + anti-CD28 mAbs; and 3) PMA + ionomycin. In marked contrast, all three mitogenic stimuli stimulated highly deficient proliferative responses by 2C+CD4+ T cells. However, significant IL-2 production was detected both in anti-CD3 and in PMA + ionomycin-stimulated cultures of 2C+CD4+ T cells. While intracellular calcium in 2C-CD4+ T cells rapidly increased following anti-CD3 addition, no such increase was observed for similarly stimulated 2C+CD4+ T cells. Anti-CD28, PMA, and coculture with 2C-CD4+ T cells each failed to significantly correct the deficient 2C+CD4+ T cells proliferation as induced by anti-CD3. In addition, IL-2, IL-4, and IL-7 supplements also failed to reverse the deficient proliferation of 2C+CD4+ T cells despite expression of IL-2R component alpha-, beta-chains and the gamma-chain common also to IL-4R and IL-7R. Thymus CD4+8- T cells from the 2C-transgenic mouse were similarly deficient in proliferation as spleen CD4+ T cells. A small subpopulation of CD4+ T cell from the 2C-transgenic mouse expressed the transgenic TCR alpha:beta heterodimer as detected by the 1B2 anti-2C clonotypic mAb; both 1B2+ and 1B2- subpopulations proliferated poorly in response to anti-CD3 and to PMA + ionomycin. These results raise the possibility that TCR engagement with MHC class 1 molecules during early intrathymic development can result in the emergence of CD4+ T cells characterized by unusual marker expression and function.
对来自MHC I类限制性2C TCR转基因（2C +）小鼠和对照转基因阴性同窝小鼠（2C -）的CD4 + T细胞的免疫功能和标志物表达进行了比较研究。虽然基于CD44高CD45RB低表达，2C + CD4 + T细胞类似于记忆T细胞，但大多数2C - CD4 + T细胞具有CD44低CD45RB高的幼稚表型。发现2C + CD4 + T细胞上的TCR-β和CD3水平略低于2C - CD4 + T细胞。在用以下物质刺激后观察到2C - CD4 + T细胞的强烈增殖：1）通过巨噬细胞的FcR呈递的抗CD3单克隆抗体；2）固定化（板结合）抗CD3 +抗CD28单克隆抗体；3）佛波酯+离子霉素。与之形成鲜明对比的是，所有三种促有丝分裂刺激均刺激2C + CD4 + T细胞产生高度缺陷的增殖反应。然而，在2C + CD4 + T细胞的抗CD3和佛波酯+离子霉素刺激的培养物中均检测到显著的IL - 2产生。在添加抗CD3后，2C - CD4 + T细胞中的细胞内钙迅速增加，而类似刺激的2C + CD4 + T细胞未观察到这种增加。抗CD28、佛波酯以及与2C - CD4 + T细胞共培养均未能显著纠正抗CD3诱导的2C + CD4 + T细胞增殖缺陷。此外，尽管表达了IL - 2R成分α链、β链以及IL - 4R和IL - 7R共有的γ链，但IL - 2、IL - 4和IL - 7补充剂也未能逆转2C + CD4 + T细胞的增殖缺陷。2C转基因小鼠的胸腺CD4 + 8 - T细胞与脾脏CD4 + T细胞一样，增殖同样缺陷。通过1B2抗2C克隆型单克隆抗体检测到，2C转基因小鼠的一小部分CD4 + T细胞表达转基因TCRα:β异二聚体；1B2 +和1B2 -亚群对抗CD3和佛波酯+离子霉素的增殖反应均较差。这些结果增加了一种可能性，即在胸腺内早期发育过程中，TCR与MHC I类分子的结合可导致出现具有异常标志物表达和功能的CD4 + T细胞。
