SPECIFIC KILLING OF CYTOTOXIC T-CELLS AND ANTIGEN-PRESENTING CELLS BY CD4+ CYTOTOXIC T-CELL CLONES - A NOVEL POTENTIALLY IMMUNOREGULATORY T-T-CELL INTERACTION IN MAN
SPECIFIC KILLING OF CYTOTOXIC T-CELLS AND ANTIGEN-PRESENTING CELLS BY CD4+ CYTOTOXIC T-CELL CLONES - A NOVEL POTENTIALLY IMMUNOREGULATORY T-T-CELL INTERACTION IN MAN
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DOI：
10.1084/jem.171.6.2011
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发表时间：
1990-06-01
影响因子：
15.3
通讯作者：
MUTIS, T
中科院分区：
文献类型：
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作者：
OTTENHOFF, THM;MUTIS, T
分枝杆菌抗原不仅刺激产生巨噬细胞活化因子的Th细胞，而且刺激裂解人巨噬细胞的CD 4+和CD 8 + CTL。分枝杆菌重组65-kD热休克蛋白以前被发现是一个重要的多克隆CD 4 + CTL的靶抗原。由于65-kD热休克蛋白在对分枝杆菌以及自身抗原的免疫应答中的主要作用，我们研究了在克隆水平上对该蛋白的CTL活性。HLA-DR或HLA-DQ限制的，识别M.麻风65-kD hsp强烈裂解用特异性但非无关肽脉冲的EBV-BLCL。未观察到B细胞、T细胞或肿瘤细胞的旁观者溶解。PMA + Ca ~（2+）离子载体不能单独触发靶细胞裂解，而依赖于活性代谢。有趣的是，这些CD 4 + CTL也强烈地裂解自身和其它HLA-II类相容性CD 4+（TCR-α/β）。β的或-γ/。delta.）或CD 8 + CTL克隆，这表明CTL没有被主动保护免于CTL介导的裂解。冷靶竞争实验表明EBV-BLCL靶比CD 4 + CTL靶更有效地被识别。这些结果表明，hsp 65肽特异性HLA II类限制性CD 4 + T细胞克隆对APC和出乎意料的CD 4+和CD 8 + CTL克隆（包括它们自身）显示出强的肽依赖性细胞溶解活性。因为，与鼠T细胞相反，人T细胞表达II类，CTL介导的T细胞杀伤可能代表了一种新的免疫调节途径。
Mycobacterial antigens not only stimulate Th cells that produce macrophage-activating factors, but also CD4+ and CD8+ CTL that lyse human macrophages. The mycobacterial recombinant 65-kD hsp was previously found to be an important target antigen for polyclonal CD4+ CTL. Because of the major role of 65-kD hsp in the immune response to mycobacterial as well as autoantigens, we have studied CTL activity to this protein at the clonal level. HLA-DR or HLA-DQ restricted, CD4+CD8- T cell clones that recognize different peptides of the M. leprae 65-kD hsp strongly lysed EBV-BLCL pulsed with specific but not irrelevant peptide. No bystander lysis of B cells, T cells, or tumor cells was seen. Target cell lysis could not be triggered by PMA + Ca2+ ionophore alone and depended on active metabolism. Interestingly, these CD4+ CTL also strongly lysed themselves and other HLA-class II compatible CD4+ (TCR-.alpha./.beta. or -.gamma./.delta.) or CD8+ CTL clones in the presence of peptide, suggesting that CTL are not actively protected from CTL-mediated lysis. Cold target competition experiments suggested that EBV-BLCL targets were more efficiently recognized than CD4+ CTL targets. These results demonstrate that hsp65 peptide-specific HLA class II-restricted CD4+ T cell clones display strong peptide-dependent cytolytic activity towards both APCs, and, unexpectedly, CD4+ and CD8+ CTL clones, including themselves. Since, in contrast to murine T cells human T cell express class II, CTL-mediated T cell killing may represent a novel immunoregulatory pathway in man.