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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Abstract
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 γ 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.