INVIVO AND INVITRO 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.