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

Eur J Immunol. 2004 Oct;34(10):2771-80. doi: 10.1002/eji.200324761.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoids / cytology
  • Adenoids / immunology
  • Adult
  • Apoptosis / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / immunology*
  • Child, Preschool
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein
  • Humans
  • Immunologic Memory
  • Infant
  • Interleukins / immunology*
  • Leukocyte Common Antigens / immunology*
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • fas Receptor / immunology


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Enzyme Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukins
  • Membrane Glycoproteins
  • fas Receptor
  • Leukocyte Common Antigens