Activation interferes with the APO-1 pathway in mature human T cells.
One of the mechanisms to terminate a specific immune response may involve elimination of antigen activated T cells by programmed cell death, apoptosis. Apoptosis in activated T cells may be induced via the TCR-CD3 complex or/and cell surface molecules like the APO-1 (Fas) antigen, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily. To investigate apoptosis in activated T cells we studied expression of APO-1 and sensitivity to APO-1 mediated apoptosis in human peripheral T lymphocytes. APO-1 is not expressed on cord blood and the majority of resting T cells, but on activated T cells. One day activated T cells in culture showed activation induced resistance to apoptosis (ARA). However, after prolonged in vitro culture, 6 day activated T cells acquired sensitivity to activation induced sensitivity to apoptosis (ASA). Restimulation of the ASA+ activated T cells by triggering TCR-CD3 or CD2 induced proliferation and apoptosis in a fraction of the cells. In the surviving fraction of ASA+ activated T cells, however, this treatment reinduced a transient ARA+ phenotype. Thus, activation of resting mature T cells or restimulation of activated T cells may induce a transient resistance to apoptotic signals. Activation signals may interfere with the APO-1 pathway and may prevent elimination of activated T cells in the periphery (peripheral selection).
Klas
C
C
Tumorimmunology Program, German Cancer Research Center, Heidelberg.
Debatin
K M
KM
Jonker
R R
RR
Krammer
P H
PH
D000954:Antigens, Surface / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor
D000954:Antigens, Surface; D019014:fas Receptor; D003609:Dactinomycin; D003513:Cycloheximide