title: Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells.
abstract: Signaling via the CD3/TCR complex induces programmed cell death (apoptosis) in immature thymocytes and transformed T lymphocytes (hybridomas or leukemic cells). Accumulating evidence indicates, however, that apoptosis can be triggered also in mature peripheral T cells. Here we show that a significant fraction of cells of a given IL-2-dependent TCR-alpha beta + clone or polyclonal short term line is killed when cultured for 20 h in the presence of PHA, anti-CD3 (OKT3), or anti-TCR (BMA031) mAb. Apoptosis can be triggered by these stimuli in CD4+, CD8+, and CD4-CD8- (double-negative) TCR-alpha beta+ clones. Activation-driven cell death (as quantified by propidium iodide staining and FACS analysis) is associated with fragmentation of DNA into oligonucleosomal bands of approximately 200 bp. Although freshly isolated peripheral blood T cells are largely resistant to apoptosis, the sensitivity to anti-CD3/TCR mAb or PHA-triggered cell death gradually increases upon activation and IL-2-dependent culture of T cells, and reaches a plateau level after 15 to 20 days. These data indicate that stimuli that activate resting T cells initiate death by apoptosis in activated T cells. The implications of these results for the regulation of cellular immune responses and the establishment of peripheral tolerance will be discussed.
authors: Institute of Immunology, University of Heidelberg, Germany.
authors: S
authors: S
authors: Wesselborg
authors: O
authors: O
authors: Janssen
authors: D
authors: D
authors: Kabelitz
mesh_terms: D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors
chemical_list: D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta