Pajusto, Mervi;
Ihalainen, Niina;
Pelkonen, Jukka;
Tarkkanen, Jussi;
Mattila, Petri S.
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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Media type:
E-Article
Title:
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
Contributor:
Pajusto, Mervi;
Ihalainen, Niina;
Pelkonen, Jukka;
Tarkkanen, Jussi;
Mattila, Petri S.
Description:
<jats:title>Abstract</jats:title><jats:p>The number of T cells that have undergone proliferation after antigen stimulation <jats:italic>in vivo</jats:italic> 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<jats:sup>+</jats:sup> CD4<jats:sup>+</jats:sup> T cells, but not adenotonsillar naive‐phenotype CD45RA<jats:sup>+</jats:sup> CD4<jats:sup>+</jats:sup> T cells, or peripheral blood naive or memory CD4<jats:sup>+</jats:sup> T cells, express high levels of activation‐associated antigens CD38, CD69, CD71, and HLA‐DR. These <jats:italic>in vivo</jats:italic>‐activated CD45R0<jats:sup>+</jats:sup> CD4<jats:sup>+</jats:sup> T cells were susceptible to spontaneous and rapid apoptosis <jats:italic>in vitro</jats:italic>. 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 <jats:italic>in vivo</jats:italic> activation of CD45R0<jats:sup>+</jats:sup> CD4<jats:sup>+</jats:sup> T cells, the cells experience a period of intrinsically elevated sensitivity to apoptosis and that multiple external signals control their survival.</jats:p>