American Journal of Infectious Diseases

Co-expression of Apoptosis-Related Molecules on Activated CD8+ CD38+ T-cells is Associated with HIV-1 Disease Progression

José W. Rodríguez, Luis A. Rodríguez, Griselle Font, Luis A. Cubano, Nawal M. Boukli, Miguel Otero, Robert Hunter, Madhavan P. Nair and Eddy Ríos-Olivares

DOI : 10.3844/ajidsp.2007.208.216

American Journal of Infectious Diseases

Volume 3, Issue 4

Pages 208-216

Abstract

CD8+ T cells play a major role in controlling HIV-1 infection through the release of soluble lytic and non-lytic antiviral factors. Their decrease or defective function contributes to the HIV-1 disease progression. HIV-1 disease progression has been associated with a remarkable increase of CD38 expression on CD8+ T-cells. It has been also documented that a significant distribution of HIV-specific CD8+T-cells resides in the CD8+CD38+ T-cell sub-population. The failure of HIV-specific CD8+CD38+ T-cells to control HIV-1 infection has been attributed to several mechanisms including apoptosis. However, the relationship between the CD38 expression and molecular events involved in CD8+ T-cell apoptosis is not well understood. Using four-color flow cytometric analysis, the present cross-sectional study we evaluated the expression of four membrane-associated apoptosis-related molecules (TNFR-1, Annexin-V, CXCR4, and CD95) and two cytoplasm-associated apoptosis-related molecules (Bcl-2 and the active form caspase-3) in 41 HIV-1 positive patients and 15 HIV-1 negative individuals. Flow cytometric analysis made on freshly isolated PBMC showed that HIV-1 infection alters the level of expression of CD38, CD95, CXCR4, Bcl-2 and active caspase-3. No significant change in the expression of Annexin V or TNFR-1 was found. A positive correlation was established between CD95, CXCR4, and active caspase-3 expression with low CD4 count and high plasma viremia and CD38 expression. Data suggest that the majority of activated CD8+CD38+ T-cells were apoptotic because they expressed active caspase-3 and the rest of these cells were highly susceptible to become apoptotic since they co-expressed CD95 and CXCR4. Results also suggest that one of the most likely HIV-mediated apoptosis mechanisms is via CD95 and CXCR4 induction through the caspase cascade despite the expression of Bcl-2. All these observations may provide an additional explanation of why HIV-1 infection is not fully contained by HIV-specific CD8+CD38+ T-cells leading to HIV-1 disease progression.

Copyright

© 2007 José W. Rodríguez, Luis A. Rodríguez, Griselle Font, Luis A. Cubano, Nawal M. Boukli, Miguel Otero, Robert Hunter, Madhavan P. Nair and Eddy Ríos-Olivares. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.