HIV-1 Viremia Prevents the Establishment of Interleukin 2-producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity

Souheil Antoine Younes, Bader Yassine-Diab, Alam R. Dumont, Mohamed Rachid Boulassel, Zvi Grossman, Jean Pierre Routy, Rafick Pierre Sékaly

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Abstract

CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester-based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA- CCR7- central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA- CCR7- effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-γ. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-γ. Longitudinal analysis of HIV epitope-specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-γ-producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2-producing CD4+ T cells and that IFN-γ only-producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-γ only-producing cells that lack self-renewal capacity.

Original languageEnglish
Pages (from-to)1909-1922
Number of pages14
JournalJournal of Experimental Medicine
Volume198
Issue number12
DOIs
Publication statusPublished - Dec 15 2003

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Keywords

  • HAART
  • Primary HIV-1 infection
  • T cell memory
  • T cell proliferation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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