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 gp120/anti-gp120 Ab primes resting T lymphocytes for activation-induced cell death (AICD) triggered via the CD3/TCR complex. In striking contrast, we demonstrate here that preincubation of activated human CD4+ T cells with anti-CD4 mAb consistently inhibited AICD triggered via anti-CD3 mAb or Staphylococcus aureus enterotoxin A superantigen. Inhibition 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, but not rIL-16, inhibited AICD stimulated by S. aureus enterotoxin A. In susceptible clones, CD4 ligation prevented the up-regulation of Fas ligand mRNA and cell surface expression in response to anti-CD3 mAb or superantigen stimulation. CD3/TCR-dependent protein tyrosine phosphorylation and cytokine production were also prevented by preceding CD4 ligation. The inhibition of AICD due to the prevention of Fas ligand upregulation reveals a novel immunoregulatory consequence of CD4 ligation that might play a role in HIV infection and in the therapeutic application of anti-CD4 mAb.
Oberg
H H
HH
Department of Immunology, Paul Ehrlich Institute, Langen, Germany.
Sanzenbacher
R
R
Lengl-Janssen
B
B
Dobmeyer
T
T
Flindt
S
S
Janssen
O
O
Kabelitz
D
D
D000906:Antibodies / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D006801:Humans; D019410:Interleukin-16 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
D000906:Antibodies; D015704:CD4 Antigens; D016207:Cytokines; D004768:Enterotoxins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D019410:Interleukin-16; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; C026066:enterotoxin A, Staphylococcal