-- Researchers in Israel have identified a potential target for treatments to help preserve immune function in HIV(+) patients.
Dr. Qibin Leng and colleagues at Hebrew University Hadassah Medical School in Rehovot conducted a study to determine "the role of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) during HIV infection."
This antigen is expressed at high levels during infection, and is associated with CD4 cell loss, Leng and coauthors found.
HIV patients carried a significantly higher proportion of CD4 cells coexpressing CTLA-4, they said. The number of CTLA-4(+) cells was negatively correlated with CD4 cell counts in all patients, regardless of their treatment history.
Peripheral blood mononuclear cell (PBMC) responses to HIV antigens were suppressed in patients with large populations of CTLA-4(+) cells, study data showed. T cells expressing this antigen showed a significant downregulation of CD28, a co-stimulatory molecule thought to prevent T-cell anergy.
CD4 cells expressing CTLA-4 were significantly more likely to express CCR5, a coreceptor used by HIV for cell entry, and the proliferation protein Ki-67 (CTLA-4 upregulation during HIV infection: association with anergy and possible target for therapeutic intervention, AIDS 2002 Mar 8;16(4):519-29.
"CTLA-4 is upregulated during HIV infection and may therefore account for CD4 T-cell decline and anergy in HIV-1 infection," Leng and colleagues concluded. "Blocking of CTLA-4 may offer a novel approach for immune-based therapy in HIV infection."
The corresponding author for this report is Dr. Zvi Bentwich, Hebrew University Jerusalem, Hadassah Medical School, Kaplan Medical Center, AIDS Center, Ruth Ben-Ari Institute of Clinical Immunology, IL-76100 Rehovot, Israel.
Key points reported in this study include:
- Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) may contribute to CD4 cell loss during HIV infection
- This antigen is strongly upregulated in T-cells from HIV patients and suppresses expression of molecules related to T-cell activation
- Peripheral blood mononuclear cell responses to HIV antigens were significantly attenuated in patients with strong CTLA-4 expression
This article was prepared by AIDS Weekly editors from staff and other reports.