期刊
PLOS ONE
卷 9, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0085613
关键词
-
资金
- National Institute of Allergy and Infectious Diseases [AI052745, AI47062, AI43864, AI055273, AI44595, P30 AI027763, R24 AI067039]
- amfAR [106710-40-RGRL]
- California AIDS Research Center [CC99-SF, ID01-SF-049]
- Center for AIDS Prevention Studies [P30 MH62246]
- Burroughs Wellcome Fund Clinical Scientist Award in Translational Research
- National Institutes of Health (NIH) Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research [DPI OD00329]
The ability to reconstitute a normal immune system with antiretroviral therapy in the setting of HIV infection remains uncertain. This study aimed to characterize quantitative and qualitative aspects of various T cell subpopulations that do not improve despite effective ART. CD4:CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/mu l (non-controllers, n = 42), those with undetectable viral loads on ART (ART-suppressed, n = 53), and HIV-uninfected subjects (n = 22). In addition, T cell phenotype and function were examined in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects. CD4:CD8 ratio in non-controllers, ART-suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with no change in the expanded CD8+ T cell population. Expansion of differentiated (CD28-CD27-CD45RA+/-CCR7-) T cell subpopulations persisted despite ART and minimal changes were noted in naive T cell frequencies over time. Increased number of CD8+CD28- T cells and increased CD8+ CMV-specific T cell responses were associated with a decreased CD4: CD8 ratio. Measures of T cell function demonstrated persistence of high frequencies of CD8+ T cells producing IFN-gamma. Lastly, though all CD8+ subpopulations demonstrated significantly lower Ki67 expression in ART-suppressed subjects, CD4+ T cell subpopulations did not consistently show this decrease, thus demonstrating different proliferative responses in the setting of T cell depletion. In summary, this study demonstrated that CD4:CD8 ratios remained significantly decreased and naive T cell numbers were slow to increase despite long-term viral suppression on ART. In addition, there is a evidence of differential regulation of the CD4+ and CD8+ T cell subpopulations, suggesting independent homeostatic regulation of the two compartments.
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