Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies.
AIDS is characterized by a progressive decline in the number of CD4+ T cells. This is preceded by an early selective defect in the proliferation of these cells to recall antigens [1-3], pokeweed mitogen (PWM) [4-6] and to superantigens (SAg) [4,7]. In contrast, the proliferative response to phytohaemagglutinin (PHA) remains intact [1,2,5]. We and others have shown that the proliferative defect in response to some stimuli was in fact due to the induction of cell death [4,7]. The activation-induced cell death mechanism that explains the proliferative defects observed in vitro might also account for the progressive in vivo deletion of CD4+ T cells. Indeed, studies performed on different models of primates have shown that induction of cell death in CD4+ T cells was detected only when T cells were isolated from animals infected with a type of retrovirus that induces an AIDS-like disease [8]. This correlation prompted us to analyse further the mechanism of HIV-induced activation cell death to determine the specificity and rate of induction of cell death. T cells from HIV-infected individuals were activated with superantigens and the V beta T cell receptor (TCR) expression analysed. Data presented here show that cell death is restricted to activated CD4+ T cells, and does not affect bystander cells. More importantly, addition of anti-CD28 MoAb specifically inhibited the induction of apoptosis, raising possibilities for therapy.
Cottrez
F
F
Unité INSERM U167, Institut Pasteur, Lille, France.
Capron
A
A
Groux
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002648:Child; D017637:Clonal Deletion; D004768:Enterotoxins / Q000494:pharmacology; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D014430:Twins, Monozygotic
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D018089:Superantigens; C031818:enterotoxin B, staphylococcal