20th International AIDS Conference - Melbourne, Australia

Abstract

MOPE013 - Poster Exhibition


Antiretroviral therapy preserves polyfunctional HIV-1-specific CD8 T cells with stem cell-like properties

S. Vigano1, J. Negron2, F. Pereyra2, E.S. Rosenberg3, M. Lichterfeld2, X. Yu2

1The Ragon Institute of MGH, MIT and Harvard, Infectious Disease, Cambridge, United States, 2The Ragon Institute of MGH, MIT and Harvard, Cambridge, United States, 3Massachussetts General Hospital, Boston, United States

Background: CD8 T stem cell memory T cells (TSCM cells) have been recently identified in humans, mice and non-human primates, and seem to represent the most immature memory CD8 T cell population with potent abilities to proliferate and repopulate the memory T cell pool. The presence and the function of CD8 TSCM cells in HIV-1 positive individuals is unknown.
Methods: CD8 T memory stem cells were analyzed in 43 HIV-1 patients (11 with HAART-treated HIV-1 infection, 18 with untreated progressive HIV-1 infection, and 14 untreated controllers with spontaneous control of HIV-1 viremia to < 1000 copies/ml). Phenotype and function of CD8 TSCM cells were assessed by flow cytometry; virus-specific CD8 T cell populations (n=32 HIV-1-specific responses, n=15 CMV/EBV/Flu-specific responses) were identified by MHC class I multimer staining or intracellular cytokine staining. 12 HIV-1 negative study subjects with n=11 CMV/EBV/Flu-specific CD8 T cell responses were analyzed as controls.
Results: Levels of TSCM in total CD8 T cells were significantly decreased in untreated HIV-1 patients (p< 0.04), but not different between HAART-treated HIV-1 patients and negative control patients. The frequency of CMV-, EBV- and Flu- specific CD8 TSCM cells in HIV-1-infected patients was similar to uninfected individuals, but significantly higher than the proportion of HIV-specific CD8 T cells in HIV-1 patients (p=0.009). Among all HIV-1 patients, HIV-1-specific CD8 TSCM cells were most frequent in HAART-treated patients (p< 0.02). Moreover, HIV-1-specific CD8 TSCM cells from these patients showed the highest degree of polyfunctionality in comparison to the other groups of patients (p< 0.03).
Conclusions: Polyfunctional HIV-1-specific CD8 TSCM cells are able to persist long-term and show a relative accumulation during antiretroviral therapy when viral antigen is pharmacologically suppressed. Due to their antigen-independent persistence in HAART-treated patients, these cells may be particularly effective in targeting the reservoir of HIV-1-infected cells after pharmacological interventions that reverse viral latency.


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