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Published on: September 24, 2010
Expression of the Fas antigen in patients infected with human immunodeficiency virus
T W McCloskey1, N Oyaizu, M Kaplan
1Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA.
Insights
HIV infection accelerates lymphocyte apoptosis. This study found increased Fas antigen expression on lymphocytes in advanced HIV disease (CDC category 3), correlating with lower CD4 T cell counts.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Lymphocytes in HIV infection show accelerated apoptosis.
- Fas antigen is a key mediator of apoptosis.
- Understanding Fas antigen expression in HIV is crucial.
Purpose of the Study:
- To investigate Fas antigen expression on lymphocytes during HIV infection.
- To correlate Fas expression with disease severity (CDC categories).
Main Methods:
- Three-color flow cytometry was used.
- Lymphocytes from 23 HIV-infected individuals and 10 healthy controls were analyzed.
- Expression of Fas antigen on CD3+CD4+ and CD3+CD8+ T cell subsets was quantified.
Main Results:
- Fas antigen expression was significantly increased on CD4+ T cells in HIV patients of CDC category 3 (CD4 < 200 cells/microL).
- Increased Fas expression on CD4+ T cells correlated with decreased CD4 T cell counts.
- Mean Fas expression per cell increased threefold on CD4+ and twofold on CD8+ T cells in category 3 patients.
Conclusions:
- HIV infection leads to increased Fas antigen expression on lymphocytes.
- Elevated Fas expression may contribute to lymphocyte apoptosis in advanced HIV disease.
Abstract:
Lymphocytes from patients with HIV infection have been shown to undergo accelerated apoptosis. Fas antigen is a cell surface protein known to initiate an apoptotic signal. Therefore, we undertook a study to examine the expression of the Fas antigen during HIV infection. Using three color flow cytometry, expression of the Fas antigen on lymphocytes of 23 HIV infected individuals (CDC category 2, CD4 200-499 cells/microL, n = 10; CDC category 3, CD4 < 200 cells/microL, n = 13) and 10 healthy controls was examined. Both CD3+CD4+ and CD3+CD8+ subsets were examined for their expression of this marker. In lymphocytes of healthy controls, 47% of the CD3+CD4+ and 45% of the CD3+CD8+ cells were Fas antigen positive. This percentage was significantly increased in CD4 cells from HIV infected patients belonging to CDC category 3, but was unchanged from normal values in CDC category 2 subjects. The increase in the percentage of CD4+ T cells expressing Fas antigen in patients correlated significantly with the decrease in circulating CD4 T cell count (P < 0.009). In addition, by examining mean fluorescence intensity, we found that the amount of Fas expression per cell was increased threefold in CD3+CD4+ cells and increased twofold in CD3+CD8+ cells in category 3 patients. These results demonstrate that an increase in Fas antigen expression occurs during HIV infection.
