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Functional restoration of human immunodeficiency virus and Epstein-Barr virus-specific CD8(+) T cells during highly active antiretroviral therapy is associated with an increase in CD4(+) T cells.

Kostense, Stefan; Otto, Sigrid A; Knol, Gerlinde J; Manting, Erik H; Nanlohy, Nening M; Jansen, Christine; Lange, Joep M A; van Oers, Marinus H J; Miedema, Frank; van Baarle, Debbie.
Eur J Immunol; 32(4): 1080-9, 2002 04.
Artigo em Inglês | MEDLINE | ID: mdl-11920575
To investigate the effect of highly active antiretroviral therapy (HAART) on HIV- and Epstein-Barr virus (EBV)-specific CD8(+) T cells, total number and function of these cells was determined in 16 HIV-infected individuals using tetrameric HLA-peptide complexes and IFN-gamma ELISPOT assays after peptide stimulation, respectively. HAART induced a significant decrease in HIV-specific tetramer(+) T cells, whereas EBV-specific tetramer(+) T cells did not change. In addition, individuals who temporarily failed on therapy showed a temporary increase in the number of HIV-specific T cells, suggesting that differences in the pool size of antigen-specific T cells was determined by the presence of antigen. Interestingly, there was an increase in the ratio of IFN-gamma-producing T cells per total number of both HIV- and EBV-specific T cells in the majority of individuals, suggesting that the function of virus-specific T cells is improved in individuals successfully treated with HAART. Despite this relative functional improvement of EBV-specific T cells, no significant changes were observed in EBV load. In four subjects who temporarily failed on HAART, the percentage of IFN-gamma-producing T cells, both for HIV and EBV, paralleled CD4(+) T cell kinetics, suggesting that function seems to be related to differences in CD4(+) T cell numbers. Overall, these data indicate that HAART improves the antigen responsiveness of both HIV- and EBV-specific T cells, which is associated with an increase in CD4(+) T cells.
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