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Progressive reduction of CMV-specific CD4+ T cells in HIV-1-Infected individuals receiving HAART V. Grosse, H. Heiken, K. Weber, M. Mendila, R. Jacobs, and R. E. Schmidt.
Dept. of Clin. Immunology, Hannover Med. Sch., Germany Background of study: Visualization of antigen-specific T cells has become an important tool in studying immune responses. The detection of antigen-specific CD4+ T cells against CMV during the HIV-1 infection can provide important insight into the role of these cells in HIV host defense.
Objective: To study frequencies of CMV-specific CD4+ T cells in healthy and HIV-infected individuals.
Design: PBMC from 5 HIV-negative and 25 HIV-positive individuals were examined for antigen-induced intracellular cytokine responses. 2 of 5 HIV-negative and 21 of 25 HIV-positive individuals were CMV+. After 6h of in vitro CMV-antigen stimulation, CD4+ CD69+ T cells were analyzed for TNFa production using flow cytometry.
Results: We found significant numbers of CMV-specific CD4+ T cells detectable in most HIV-1 infected individuals after 6h in vitro antigen stimulation with CMV antigen. CMV-specific CD4+ T cells were detectable in healthy HIV- CMV+ individuals at a frequency of 0.27% and 0.04%, respectively. CMV-specific CD4+ T cells could not be demonstrated in healthy HIV- CMV- and HIV+ CMV- individuals. Median frequencies of CMV-specific CD4+ T cells were lower in long term nonprogressors (LTNP) (1.49%) than in untreated, progressive HIV-infected, CMV+ individuals (2.88%), but higher than in HIV-infected subjects, who had been treated with highly active antiretroviral therapy (HAART) (0.49%). In subjects treated for less than 1 year the median CMV-specific CD4+ T-cell responder frequencies were higher (0.63%) than in subjects treated for more than 1 year (0.41%).
Conclusions: Antigen specific CD4+ T cells reactive against CMV-specific antigens can be detected in the majority of HIV-infected patients. HIV suppression with HAART may lead to a progressive reduction in median frequencies of CMV-specific CD4+ T cells. These data might indicate an efficient elimination of the CMV pathogen.
Key Words: CD4, CMV, HIV
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