HIV-1 gp120 accelerates Fas-mediated activation-induced human lamina propria T cell apoptosis

Area of Science:

• Immunology
• Virology
• Gastroenterology

Background:

• The intestinal mucosa is a primary site for HIV entry, replication, and reservoir formation.
• Early depletion of intestinal lamina propria T lymphocytes (LPT) is observed in HIV patients.
• HIV-1 gp120 is known to induce apoptosis in peripheral blood T cells.

Purpose of the Study:

• To investigate whether HIV-1 gp120 modulates apoptosis in normal human intestinal lamina propria T cells.
• To determine the mechanism by which gp120 affects LPT cell viability.

Main Methods:

• Purification of T cells from human lamina propria mononuclear cells using immunomagnetic negative selection.
• Incubation of purified LPT cells with recombinant HIV-1 gp120.
• Stimulation of T cells with anti-CD3 or anti-CD2 antibodies.
• Assessment of apoptosis via flow cytometry and propidium iodide staining.
• Analysis of Fas/Fas ligand interaction and Fas ligand mRNA induction.

Main Results:

• HIV-1 gp120 preincubation accelerated apoptosis in LPT cells stimulated via the CD2 pathway.
• This gp120-induced apoptosis was mediated by Fas/Fas ligand interaction.
• gp120 increased the induction of Fas ligand mRNA in LPT cells.

Conclusions:

• HIV-1 gp120 contributes to the depletion of noninfected intestinal lamina propria T cells.
• gp120 induces premature cell death in LPT cells, potentially through Fas/Fas ligand pathways.
• This mechanism may play a significant role in the immunopathology of HIV in the gut.