title: IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes.
abstract: In recent years, several studies have confirmed the clonal elimination of thymocytes with receptors that recognize Ag and MHC molecules present on the membrane of thymic stromal cells, a process that may be relevant to the establishment of self-tolerance. In our work, we show that anti-CD3 treatment of single positive CD4+ or CD8+ human medullary thymocytes (obtained by anti-CD1a plus C) induces their apoptotic death. Some events commonly associated with the early steps of normal activation (IL-2R expression, increase in cytoplasmic Ca2+) are also induced after anti-CD3 treatment. Nevertheless, IL-2 is not secreted by these activated cells. The addition of exogenous IL-2 inhibits the apoptosis induced by anti-CD3. We suggest that the lack of secretion of IL-2 by medullary thymocytes may be a physiologic mechanism implicated in the process of negative selection that leads to tolerance.
authors.affiliation: Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Nieto
authors.forename: A
authors.initials: A
authors.lastname: González
authors.forename: A
authors.initials: A
authors.lastname: López-Rivas
authors.forename: F
authors.initials: F
authors.lastname: Diaz-Espada
authors.forename: F
authors.initials: F
authors.lastname: Gambón
mesh_terms: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D002118:Calcium / Q000502:physiology; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D004247:DNA; D002118:Calcium