Human in vivo-activated CD45R0+ CD4+ T cells are susceptible to spontaneous apoptosis that can be inhibited by the chemokine CXCL12 and IL-2,-6,-7, and-15
Human in vivo-activated CD45R0+ CD4+ T cells are susceptible to spontaneous apoptosis that can be inhibited by the chemokine CXCL12 and IL-2,-6,-7, and-15
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DOI：
10.1002/eji.200324761
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Mattila, PS
中科院分区：
文献类型：
--
作者：
Pajusto, M;Ihalainen, N;Mattila, PS
必须控制体内抗原刺激后发生增殖的T细胞数量，防止T细胞过度积累、自身免疫和T细胞瘤的发生。我们在这里描述了原发性人腺扁桃体记忆表型CD45R0(+) CD4(+) T细胞，而不是腺扁桃体幼稚表型CD45RA(+) CD4(+) T细胞，或外周血幼稚或记忆CD4(+) T细胞，表达高水平的活化相关抗原CD38， CD69， CD71和HLA-DR。这些体内活化的CD45R0(+) CD4(+) T细胞在体外易发生自发和快速凋亡。细胞凋亡不能通过破坏Fas-Fas配体结合或泛caspase抑制剂ZVAD来抑制。T细胞抗原受体的交联不能使细胞免于凋亡。趋化因子CXCL12/SDF-1、IL-6和IL-2受体常见γ链信号细胞因子IL-2、-7和-15可部分抑制细胞凋亡。磷脂酰肌醇3-激酶抑制剂加速细胞凋亡。我们得出结论，在体内激活CD45R0(+) CD4(+) T细胞后，细胞会经历一段对凋亡的内在敏感性升高的时期，并且多种外部信号控制着它们的生存。
The number of T cells that have undergone proliferation after antigen stimulation in vivo must be controlled to prevent excessive accumulation of T cells, autoimmunity, and T cell neoplasia. We describe here that primary human adenotonsillar memory phenotype CD45R0(+) CD4(+) T cells, but not adenotonsillar naive-phenotype CD45RA(+) CD4(+) T cells, or peripheral blood naive or memory CD4(+) T cells, express high levels of activation-associated antigens CD38, CD69, CD71, and HLA-DR. These in vivo-activated CD45R0(+) CD4(+) T cells were susceptible to spontaneous and rapid apoptosis in vitro. Apoptosis could not be inhibited by the disruption of Fas-Fas ligand engagement or by the pan-caspase inhibitor ZVAD. Cross-linking of the T cell antigen receptor did not rescue cells from apoptosis. Apoptosis could be partially inhibited by the chemokine CXCL12/SDF-1, by IL-6, and by the IL-2 receptor common gamma chain-signaling cytokines IL-2, -7, and -15. Inhibitors of phosphatidylinositol 3-kinase accelerated apoptosis. We conclude that after in vivo activation of CD45R0(+) CD4(+) T cells, the cells experience a period of intrinsically elevated sensitivity to apoptosis and that multiple external signals control their survival.