Piccolella E, Tuosto L, Somma F, Gilardini Montani MS, Di Somma MM; International Conference on AIDS.

Int Conf AIDS. 2000 Jul 9-14; 13: abstract no. TuPeA3116.

E. Piccolella, University "La Sapienza" of Rome, Dept. Cellular and Developmental Biology, Via Degli Apuli 1, 00185 Rome, Italy, Tel.: +39 6 4991 7584, Fax: +39 6 4991 7594, E-mail: piccolella@axcasp.caspur.it

Background: Since 1992, when it was demonstrated that CD4 cross-linking by HIV glicoprotein 120 (gp120) prior to activation via the TCR results in apoptotic cell death, several experimental data have been accumulated. However, a crytical analysis of these results show many discrepancies.Starting from our experience on the signals that regulate in human CD4+ memory T lymphocytes the susceptibility or the resistance to apoptosis (J. Immunol. 1999, 162: 3851ndash;3858), we tried to elucidate whether the gp120-dependent apoptosis depends from Fas- and/or Bax-dependent apoptotic pathways. Methods: We used an experimental system of viral and alloantigen-specific T cell lines and clones treated with recombinant HIV gp120 or Leu3a mAb and activated by the specific antigen. The cells, induced to apoptosize by gp120 in the presence or absence of anti-Fas agonistic mAb, were analyzed for the expression of proapoptotic and antiapoptotic genes and proteins such as Bcl-2, Bcl-xL, Bax, Flip, Fas and Fas ligand (L). The variation in the mitochondrial transmembrane electrical potential was also analyzed. Results: Our results demonstrate that gp120-induced apoptosis is associated to i) the increase of Bax expression and mitochondrial damage, ii) an inhibition of FasL and Flip expression and iii) an increase to Fas-dependent apoptosis. Furthermore, the analysis of the mechanisms by which IL-2 and IL-4 cytokines exert antiapoptotic effect on CD4+ T cells in the presence of gp120 shows that they were able to revert the susceptibility to Bax-mediated but not to CD95-dependent apoptotic pathways. Conclusions: Our message is that gp120-engaged CD4+ T cells can both suicide in a Fas-independent manner as well as to be killed in a Fas-dependent manner by bystander FasL+ cells. IL-2 treatment modifying Bcl-2/Bax ratio rescues CD4+ T lymphocytes from Fas-independent apoptosis but does not restore Flip expression and consequently does not abolish the susceptibility to Fas-dependent apoptosis.

Publication Types:

• Meeting Abstracts

Keywords:

• Antibodies, Monoclonal
• Antigens, CD4
• Antigens, CD95
• Apoptosis
• CASP4 protein, human
• CASP8 and FADD-Like Apoptosis Regulating Protein
• CD4-Positive T-Lymphocytes
• Caspases
• Fas Ligand Protein
• HIV Envelope Protein gp120
• HIV Infections
• Humans
• Interleukin-2
• Interleukin-4
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogenes
• Receptors, Antigen, T-Cell
• T-Lymphocytes
• genetics
• immunology

Other ID:

• GWAIDS0001471

UI: 102238962

From Meeting Abstracts