Direct and indirect mechanisms mediating apoptosis during HIV infection: contribution to in vivo CD4 T cell depletion

Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells

“…Cytolysis of HIV-1-infected CD4 cells and MDMs was greater than expected from the amount of viruses used for infection and the duration of infection before various assays. It is well known that HIV-1 promotes cell death in uninfected bystander cells through multiple mechanisms [28,29], including secretion of soluble factors [30], cell-tocell fusion [31] and up-regulation of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) [32]. While our cell lysis assays might have over-estimated the extent of NK cell-mediated killing, it is highly unlikely that the uniform experimental conditions could impact cells differentially based on their P2 genotypes.…”

Productive infection and subsequent interaction of CD4-gp120 at the cellular membrane is required for HIV-induced apoptosis of CD4+ T cells

“…In addition to immune-based mechanisms such as cytotoxic T cell killing (Zarling et al, 1990), natural killer cell-mediated killing of infected cells (Brenner et al, 1989) and antibody-dependent cellular cytotoxicity (Tanneau et al, 1990), HIV-induced apoptosis may also contribute to this depletion. Several mechanisms have been proposed to explain how HIV-1 infection leads to apoptotic cell death (Ameisen, 1994;Ameisen & Capron, 1991 ;Banda et al, 1992;Gougeon et al, 1993a;Groux et al, 1992;Laurent-Crawford et al, 1991;Meyaard et al, 1992;Terai et al, 1991); however, some uncertainty remains concerning the factors and pathways that trigger this process Cohen, 1993;Gougeon et al, 1993b;Gougeon & Montagnier, 1993;Weiss, 1993). A recent report from Laurent-Crawford and collaborators concluded that HIV-induced apoptosis of infected CD4 + T cells is due to gpl20-gp41 heterodimer complex programming death in these lymphocytes.…”

Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3ζ and CD28, Key Signaling Molecules for T-Cell Activation

“…A large fraction of circulating CD8 T cells in HIV-infected donors are already activated, as evidenced by high levels of expression of CD38, HLA-DR, and CD57 and the cytolytic serine esterase granzyme A (9,14,16,45,58,60). Moreover, there is a good correlation in circulating CD8 T cells (but not in lymph node T cells [2]) between granzyme A and perforin expression (L. W. Kam and J. Lieberman, unpublished data).…”