The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.
The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory.
复制标题
DOI：
10.1084/jem.178.2.427
复制
发表时间：
1993-08-01
期刊：
影响因子：
--
通讯作者：
Janossy G
中科院分区：
文献类型：
--
作者：
Akbar AN;Borthwick N;Salmon M;Gombert W;Bofill M;Shamsadeen N;Pilling D;Pett S;Grundy JE;Janossy G
bcl-2基因产物已显示出防止凋亡性细胞死亡。我们现在已经研究了静息和活化的成熟T细胞群体的bcl-2蛋白表达。CD 4+和CD 8+亚群中新鲜分离的CD 45 RO + T细胞表达的bcl-2显著低于CD 45 RO-（CD 45 RA+）T细胞（p < 0.001）。当CD 4+和CD 8+亚群中的CD 45 RA + T细胞在体外被激活时，向CD 45 RO表型的转变与bcl-2表达的降低相关。急性病毒感染如EB病毒感染引起的传染性单核细胞增多症或水痘带状疱疹病毒感染引起的水痘患者，其循环中活化的CD 45 RO + T细胞群也显示低bcl-2表达。在这些患者中，活化T细胞的低bcl-2表达与其在培养中的凋亡之间存在显著相关性（r = 0.94，p < 0.001）。这些结果表明，T细胞的初级激活导致了一个注定要灭亡的群体的扩张，除非被一些外在事件拯救。因此，自杀的CD 45 RO + T细胞可以防止通过添加白细胞介素2的培养基中，导致在这些细胞的bcl- 2表达的伴随增加。另外，细胞凋亡也被阻止通过共培养的活化的T淋巴细胞与成纤维细胞，这保持了淋巴细胞的活力在restinglike状态，但低bcl-2表达。CD 45 RO+细胞群中含有致敏/记忆T细胞库，但表达低bcl-2，易受凋亡的影响，这一矛盾可以通过观察到T细胞记忆的维持可能依赖于T细胞的持续再刺激（这增加了它们的bcl-2表达）而得到调和。此外，CD 45 RO + T细胞外渗的倾向可能有助于与组织基质中的成纤维细胞样细胞相遇，因此是促进所选的致敏/记忆T细胞体内存活的重要额外因素。
The bcl-2 gene product has been shown to prevent apoptotic cell death. We have now investigated the bcl-2 protein expression by resting and activated mature T cell populations. Freshly isolated CD45RO+ T cells within CD4+ and CD8+ subsets expressed significantly less bcl-2 than CD45RO- (CD45RA+) T cells (p < 0.001). When CD45RA+ T cells within both CD4+ and CD8+ subsets were activated in vitro, the transition to CD45RO phenotype was associated with a decrease in bcl-2 expression. Patients with acute viral infections such as infectious mononucleosis caused by Epstein-Barr virus infections or chickenpox, resulting from varicella zoster virus infection, had circulating populations of activated CD45RO+ T cells which also showed low bcl-2 expression. In these patients, a significant correlation was seen between low bcl-2 expression by activated T cells and their apoptosis in culture (r = 0.94, p < 0.001). These results suggest that the primary activation of T cells leads to the expansion of a population that is destined to perish unless rescued by some extrinsic event. Thus the suicide of CD45RO+ T cells could be prevented by the addition of interleukin 2 to the culture medium which resulted in a concomitant increase in the bcl- 2 expression of these cells. Alternatively, apoptosis was also prevented by coculturing the activated T lymphocytes with fibroblasts, which maintained the viability of lymphoid cells in a restinglike state but with low bcl-2 expression. The paradox that the CD45RO+ population contains the primed/memory T cell pool yet expresses low bcl-2 and is susceptible to apoptosis can be reconciled by the observations that maintenance of T cell memory may be dependent on the continuous restimulation of T cells, which increases their bcl-2 expression. Furthermore, the propensity of CD45RO+ T cells to extravasate may facilitate encounter with fibroblast-like cells in tissue stroma and thus be an important additional factor which promotes the survival of selected primed/memory T cells in vivo.