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Molecule Involved in T Cell 'Exhaustion' in HIV

Blocking function of molecule restores some T cell function

THURSDAY, Aug. 24 (HealthDay News) -- Blocking the function of a molecule found at high levels on HIV-specific CD8+ T cells restores some T cell function and helps overcome the T cell "exhaustion" observed during chronic HIV infection, according to two studies published online Aug. 20 in Nature Medicine and Nature.

In the Nature Medicine study, Rafick-Pierre Sekaly, M.D., of University of Montreal in Quebec, Canada, and colleagues examined the expression of programmed death-1 (PD-1), a negative regulator of T cell function, on HIV-specific CD8+ T cells. They found high levels of PD-1 on these cells from HIV-infected viremic individuals. These cells were impaired in their ability to proliferate and produce cytokines, and blocking the interaction of PD-1 with its ligand PD-L1 restored the ability of these cells to survive and proliferate in response to antigen.

In the Nature study, Bruce D. Walker, M.D., from Massachusetts General Hospital in Boston, and colleagues also examined PD-1 expression on HIV-specific CD8+ and CD4+ T cells from HIV-positive individuals who had not yet received any HIV treatment. They found that PD-1 was upregulated on both types of cells, which correlated positively with plasma viral load and inversely with CD4+ T cell count. Blocking the interaction of PD-1 with PD-L1 with an antibody increased CD4+ and CD8+ T cell function, according to the study.

"These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function," Walker and colleagues concluded. "Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection."

Abstract - Sekaly
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Abstract - Walker
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