CD4 + T-cell differentiation, regulatory T cells and gag-specific T lymphocytes are unaffected by CD4-guided treatment interruption and therapy resumption

Elisa Nemes, Enrico Lugli, Linda Bertoncelli, Milena Nasi, Marcello Pinti, Serena Manzini, Francesca Prati, Lisa Manzini, Cinzia Del Giovane, Roberto D'Amico, Andrea Cossarizza, Cristina Mussini

Research output: Contribution to journalArticle

Abstract

Objectives: Despite limiting exposure to antiretroviral drugs, structured treatment interruptions can influence multiple aspects of T-cell immunity, particularly those regarding CD4 T lymphocytes. We evaluated the impact of CD4 +-guided treatment interruption (CD4 +-GTI) and treatment resumption on regulatory T cells (Tregs), T-lymphocyte activation, differentiation and polyfunctional gag-specific response. Methods: Patients were analyzed just prior to treatment interruption, at 2 and 6 months after treatment interruption, just prior to treatment resumption and at 2 and 6 months after treatment resumption. Thawed peripheral blood mononuclear cells were stained immediately for phenotype analysis or stimulated with HIV-gag peptides and analyzed by polychromatic flow cytometry. RESULTS:: Treatment interruption resulted in a CD4 + cell count decrease and plasma viral load (pVL) increase, but did not preclude a good immune reconstitution and a complete suppression of pVL after treatment resumption. Treatment interruption did not influence CD4 + T-cell differentiation and Treg subsets. During treatment interruption, gag-specific CD4 + T cells were not lost, although the frequency of HIV-specific CD8 cells increased. Most gag-specific CD4 + T cells were potentially cytotoxic (CD107a) and were not influenced by pVL or by HAART. Most helper (CD154) gag-specific CD4 + T lymphocytes did not produce interferon-γ or interleukin-2. Conclusion: CD4 +-GTI did not cause depletion of memory cells, Tregs or HIV-specific CD4 + cells and, on the contrary, could induce HIV-specific responses. If guided by CD4 + T-cell count, treatment interruption does not provoke irreversible immune damages.

Original languageEnglish
Pages (from-to)1443-1453
Number of pages11
JournalAIDS (London, England)
Volume25
Issue number12
DOIs
Publication statusPublished - Jul 31 2011

Keywords

  • CD4-guided treatment interruptions
  • chronic HIV infection
  • gagspecific response
  • regulatory T cells
  • T-cell activation
  • T-cell differentiation
  • T-cell polyfunctionality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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