Reconstitution of Peripheral T Cells by Tissue-Derived CCR4+ Central Memory Cells Following HIV-1 Antiretroviral Therapy.
BACKGROUND
Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4+T-cell counts, as well as a reduction in the activation status of both CD4+and CD8+T cells.


METHODS
We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4+and CD8+T cells in patients with advanced disease. We also measured gene expression by single cell transcriptomics to assess functional state.


RESULTS
The cytokine pattern of HIV-specific CD8+T cells was not altered after ART, though their magnitude decreased significantly as the plasma viral load was suppressed to undetectable levels. Importantly, while CD4+T cell numbers increased substantially during the first year, the population did not normalize: the increases were largely due to expansion of mucosal-derived CCR4+CD4+TCM; transcriptomic analysis revealed that these are not classical Th2-type cells.


CONCLUSIONS
The apparent long-term normalization of CD4+T-cell numbers following ART does not comprise a normal balance of functionally distinct cells, but results in a dramatic Th2shift of the reconstituting immune system.
ImmunoTechnology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD.
Yolanda D
YD
Mahnke
Immunology Core Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD.
Kipper
K
Fletez-Brant
Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD.
Irini
I
Sereti
ImmunoTechnology Section, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD.
Mario
M
Roederer
Cytokines; Immune reconstitution; Polarization; T helper subsets