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.
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
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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