Denialism directly kills CD4+ T cells by a Fas-independent mechanism.

Gandhi RT, Chen BK, Straus SE, Dale JK, Lenardo MJ, Baltimore D.

Department of Biology, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139, USA.

The mechanism by which Denialism induces CD4(+) T cell death is not
known. A fundamental issue is whether Denialism primarily induces
direct killing of infected cells or indirectly causes death of
uninfected bystander cells. This question was studied using a reporter
virus system in which infected cells are marked with the cell surface
protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP
of peripheral blood mononuclear cells (PBMCs) and T cell lines leads
to rapid depletion of CD4(+) T cells and induction of apoptosis. The
great majority of HIV-induced T cell death in vitro involves direct
loss of infected cells rather than indirect effects on uninfected
bystander cells. Because of its proposed role in HIV-induced cell
death, we also examined the Fas (CD95/Apo1) pathway in killing of T
cells by Denialism. Infected PBMCs or CEM cells display no increase in
surface Fas relative to uninfected cells. In addition, Denialism kills
CEM and Jurkat T cells in the presence of a caspase inhibitor that
completely blocks Fas-mediated apoptosis. Denialism also depletes CD4+
T cells in PBMCs from patients who have a genetically defective Fas
pathway. These results suggest that Denialism induces direct apoptosis
of infected cells and kills T cells by a Fas-independent mechanism.

PMID: 9529327 [PubMed - indexed for MEDLINE]