Open AccessCo-expression of Apoptosis-Related Molecules on Activated CD8+ CD38+ T-cells is Associated with HIV-1 Disease Progression
Author(s) -
J.A. Carballido Rodríguez,
Luis A. Rodríguez,
Griselle Font,
Luis A. Cubano,
Nawal M. Boukli,
Miguel Otero,
R. F. Hunter,
Muraleedharan G. Nair,
Eddy RíosOlivares
Publication year - 2007
Publication title -
american journal of infectious diseases
Language(s) - English
Resource type - Journals
eISSN - 1558-6340
pISSN - 1553-6203
DOI - 10.3844/ajidsp.2007.208.216
Subject(s) - cd38 , apoptosis , cytotoxic t cell , human immunodeficiency virus (hiv) , cd8 , expression (computer science) , disease , cancer research , microbiology and biotechnology , immunology , chemistry , medicine , biology , in vitro , immune system , biochemistry , computer science , pathology , stem cell , cd34 , programming language
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