LIGATION OF CELL-SURFACE CD4 INHIBITS ACTIVATION-INDUCED DEATH OF HUMAN T-LYMPHOCYTES AT THE LEVEL OF FAS LIGAND EXPRESSION

Cross-linking of cell surface CD4 molecules by anti-CD4 mAb or HIV-1 g p120/anti-gp120 Ab primes resting T lymphocytes for activation-induced cell death (AICD) triggered via the CD3/TCR complex. In striking cont rast, we demonstrate here that preincubation of activated human CD4(+) T cells with anti-CD4 mAb consistently inhibited AICD triggered via a nti-CD3 mAb or Staphylococcus aureus enterotoxin A superantigen. Inhib ition of AICD of CD4(+) T cell clones was also observed with F(ab')(2) , but not with Fab, of anti-CD4 mAb. Moreover, soluble HIV-1 gp120, bu t not rIL-16, inhibited AICD stimulated by S. aureus enterotoxin A. In susceptible clones, CD4 ligation prevented the up-regulation of Fas l igand mRNA and cell surface expression in response to anti-CD3 mAb or superantigen stimulation. CD3/TCR-dependent protein tyrosine phosphory lation and cytokine production were also prevented by preceding CD4 li gation. The inhibition of AICD due to the prevention of Fas ligand up- regulation reveals a novel immunoregulatory consequence of CD4 ligatio n that might play a role in HIV infection and in the therapeutic appli cation of anti-CD4 mAb.