Ligation of either CD2 or CD28 rescues CD4+ T cells from HIV-gp120-induced apoptosis.
Temporal or quantitative imbalance in signals delivered to T cells via T cell antigen receptor (TCR), the CD4 co-receptor, and accessory molecules can lead to anergy, apoptosis, or both. This has been observed following ligation of CD4 by HIV gp120 prior to TCR occupancy. The ability of molecules such as CD2 and CD28, interacting with their ligands LFA-3 and B7, to provide signals that protect T cells from the induction of anergy, has been reported. Here, we demonstrate that ligation of CD2 and CD28 in conjunction with TCR occupancy rescue T cells that have been programmed for apoptotic death by prior CD4 ligation to gp120. This appears to be the result of augmented interleukin-2 and interleukin-4 release by the T cells following these molecular interactions. In conclusion, our results suggest that an impairment of antigen-presenting accessory cell functions could favor gp120-mediated apoptosis in HIV-uninfected cells.
Tuosto
L
L
Department of Cellular and Developmental Biology, University La Sapienza, Rome, Italy.
Piazza
C
C
Moretti
S
S
Modesti
A
A
Greenlaw
R
R
Lechler
R
R
Lombardi
G
G
Piccolella
E
E
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D018801:CD2 Antigens / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018968:CD58 Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1 / Q000502:physiology*; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D007739:L Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D018968:CD58 Antigens; D015699:HIV Envelope Protein gp120; D015798:HLA-DR1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007376:Interleukin-2; D008024:Ligands; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015847:Interleukin-4