In vivo and in vitro death of mature T cells induced by separate signals to CD4 and alpha beta TCR.
To investigate whether a clonal deletion mechanism is responsible for the mature T cell tolerance that may be induced in vivo by TCR signal to anti-CD4 (H129.19 mAb) coated cells, we analyzed the T cell repertoire in anti-CD4 mAb treated BALB/c mice by flow cytometry following TCR signals through anti-alpha beta TCR mAb or SEB superantigen. Lymph nodes showed a strong reduction in the CD4+/CD8+ cell ratio, and a selective clonal loss of CD4+ V beta 8+ cells 4d following anti-alpha beta TCR or SEB injection, respectively. Following lymph node cell activation in a short-term in vitro assay with SEB or anti-V beta 8 mAb, a selective elimination of CD4+ V beta 8+ cells was again detected, and DNA fragmentation analysis disclosed a cell death by apoptosis. These findings suggest that TCR triggering transduces an apoptotic signal into CD4+ mAb saturated cells that in turn leads to specific holes in the mature T cell repertoire.
Facchinetti
A
A
Institute of Oncology, University of Padova, Italy.
Panozzo
M
M
Pertile
P
P
Tessarollo
L
L
Biasi
G
G
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology*; D016923:Cell Death / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D005434:Flow Cytometry; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D015704:CD4 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta