IL-2 protects against anti-CD3-induced cell death in human medullary thymocytes.
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.
Nieto
M A
MA
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
González
A
A
López-Rivas
A
A
Diaz-Espada
F
F
Gambón
F
F
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*
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