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.
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 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.
authors.affiliation: Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Mervi
authors.initials: M
authors.lastname: Pajusto
authors.forename: Niina
authors.initials: N
authors.lastname: Ihalainen
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
authors.forename: Jussi
authors.initials: J
authors.lastname: Tarkkanen
authors.forename: Petri S
authors.initials: PS
authors.lastname: Mattila
mesh_terms: D000234:Adenoids / Q000166:cytology / Q000276:immunology; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology*; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D007378:Interleukins / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007378:Interleukins; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens