Piccolella E, di Somma MM, Somma F, Gilardini Montani MS; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 272 (abstract no. 21166).
BACKGROUND: We have recently published that the susceptibility to gp120-mediated apoptosis of CD4+ T lymphocytes repeatedly antigen stimulated is regulated by bcl-2 expression, cell cycle progression and costimulatory signals but not by Fas expression. However, Fas pathway activation has been described as responsible, at least in part, of apoptotic phenomena in HIV-infected individuals. All together these results drove us to hypothesize that both Fas-dependent and -independent apoptotic pathways could mediate apoptosis in AIDS. METHODS: We tested this hypothesis by using CD4+ T cell clones, induced to apoptosize by antigen specific activation following pretreatment with soluble gp120. Fas and fasL mRNA expression by RT-PCR, Fas-mediated apoptosis by agonistic antibodies or soluble recombinant FasL or FasL+ bystander cells, caspase activity by western blot and mitochondrial membrane potential by fluorescent probe JC-1 were analyzed in these cells. Moreover the protective role of IL-2 and IL-4 was also investigated in the same system. RESULTS: We demonstrated that: a) the interaction of gp120 with CD4 inhibits FasL expression and favors Fas-mediated activation signals, b) gp120 mediates apoptotic programs by a caspase independent way, unless Fas molecules are triggered by specific ligands, and c) mitochondrial damage is involved in Fas-independent apoptotic pathway. CONCLUSION: Our data indicate that gp120 programs CD4+ T cells to apoptosis both via a caspase independent mechanism, inhibited by IL-2 and IL-4 mediated bcl-2 increase, and via a caspase dependent mechanism triggered by FasL+ bystander cells.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antigens, CD4
- Apoptosis
- CASP4 protein, human
- CD4-Positive T-Lymphocytes
- Caspases
- Fas Ligand Protein
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seropositivity
- Interleukin-2
- Interleukin-4
- Membrane Glycoproteins
- T-Lymphocytes
- immunology
Other ID:
UI: 102228704
From Meeting Abstracts