T cell receptor/CD3-signaling induces death by apoptosis in human T cell receptor gamma delta + T cells.
mAb directed against the TCR/CD3 complex activate resting T cells. However, TCR/CD3 signaling induces death by apoptosis in immature (CD4+CD8+) murine thymocytes and certain transformed leukemic T cell lines. Here we show that anti-TCR and anti-CD3 mAb induce growth arrest of cloned TCR-gamma delta + T cells in the presence of IL-2. In the absence of exogenous IL-2, however, the very same anti-TCR/CD3 mAb stimulated gamma delta (+)-clones to proliferation and IL-2 production. In the presence of exogenous IL-2, anti-TCR/CD3 mAb induced the degradation of DNA into oligosomal bands of approximately 200 bp length in cloned gamma delta + T cells. This pattern of DNA fragmentation is characteristic for the programmed cell death termed apoptosis. These results demonstrate that TCR/CD3 signaling can induce cell death in cloned gamma delta + T cells. In addition, this report is the first to show that apoptosis triggered by TCR/CD3 signaling is not restricted to CD4+CD8+ immature thymocytes and transformed leukemic T cell lines but can be also observed with IL-2-dependent normal (i.e., TCR-gamma delta +) T cells.
Janssen
O
O
Institute of Immunology, University of Heidelberg, Federal Republic of Germany.
Wesselborg
S
S
Heckl-Ostreicher
B
B
Pechhold
K
K
Bender
A
A
Schondelmaier
S
S
Moldenhauer
G
G
Kabelitz
D
D
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D002470:Cell Survival; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D004249:DNA Damage; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D004247:DNA