T-CELL ANTIGEN RECEPTOR ENGAGEMENT ABROGATES CD4-MEDIATED T-CELL DELETION IN-VIVO

We have previously shown that the engagement of CD4 by specific antibo dy in the mouse initiates a T cell apoptosis response with the followi ng features: spleen and lymph node CD4(+) T cells migrate into the blo odstream within minutes of anti-CD4 administration where they exhibit the phenotype of null cells. If they are capable of expressing functio nal Fas protein on their surface they degrade their DNA and disintegra te rapidly. We show here that the engagement of the T cell antigen rec eptor blocks the CD4-mediated deletion process in mouse. Anti-CD4-reac tive T cells avoid the exodus into the bloodstream when their TCR is e ngaged by anti-CD3 or by a superantigen, do not modulate surface recep tors and are not deleted. In contrast to the apoptosis-inducing CD4-sp ecific antibody which causes migration of lymphocytes from lymphoid or gans into the blood stream, the T cell-activating CD3-specific antibod y causes lymphoid cell redistribution in the opposite direction, from the bloodstream to lymphoid organs. The TCR-mediated protection of T c ells against CD4-mediated deletion lasts for several hours but ceases before the T cells become blasts.