Research Article Open Access

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

José W. Rodríguez1, Luis A. Rodríguez1, Griselle Font1, Luis A. Cubano1, Nawal M. Boukli1, Miguel Otero1, Robert Hunter1, Madhavan P. Nair2 and Eddy Ríos-Olivares1
  • 1 Universidad Central del Caribe School of Medicine, United States
  • 2 Florida International University College of Medicine, United States

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.

American Journal of Infectious Diseases
Volume 3 No. 4, 2007, 208-216

DOI: https://doi.org/10.3844/ajidsp.2007.208.216

Submitted On: 21 June 2007 Published On: 31 December 2007

How to Cite: Rodríguez, J. W., Rodríguez, L. A., Font, G., Cubano, L. A., Boukli, N. M., Otero, M., Hunter, R., Nair, M. P. & Ríos-Olivares, E. (2007). Co-expression of Apoptosis-Related Molecules on Activated CD8+ CD38+ T-cells is Associated with HIV-1 Disease Progression. American Journal of Infectious Diseases, 3(4), 208-216. https://doi.org/10.3844/ajidsp.2007.208.216

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Keywords

  • Human Immunodeficiency virus-1 (HIV-1)
  • CD8+CD38+ T-cells
  • apoptosisrelated molecules
  • four-color flow cytometry