Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART

Giulia Marchetti, Lidia Gazzola, Daria Trabattoni, Francesca Bai, Giuseppe Ancona, Laurenzia Ferraris, Luca Meroni, Massimo Galli, Mario Clerici, Andrea Gori, Antonella D'Arminio Monforte

Research output: Contribution to journalArticle

Abstract

Objective: Analysis of functionally defined T-cell differentiation in HIV-infected patients with low CD4 on virologically suppressive HAART is crucial to design clinically efficacious treatments. Methods: We cross-sectionally investigated the maturation (CD45RA/CCR7, CD7) and function [antigen-specific enzyme-linked immunosorbent spot assay (ELISPOT), interleukin-2 (IL-2)/interferon-γ-producing cells] of CD4 and CD8+ T cells in 34 HIV-infected immunological nonresponders (INRs): CD4 cell count less than or equal to 200 cells/μl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4 > 500 cells/μl, HIV-RNA <50 copies/ml). Results: We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RACCR7 CD4/CD8+ and Th2-committed CD7CD4, and reduced unprimed-naive T cells (P = 0.001). Functionally, INRs display reduced Gag-specific ELISPOT (P = 0.04) and IL-2-secreting CD8+ (P = 0.08) while showing CMV-specific responses comparable to full responders. Conclusion: CD4 lymphopenia on HAART results in skewed, senescent T-cell maturation profile, inefficient T-helper function and poor HIV-specific CD8+ response. This delineates a functional/phenotypic T-cell pattern that correlates to unfavourable clinical outcome.

Original languageEnglish
Pages (from-to)1455-1460
Number of pages6
JournalAIDS (London, England)
Volume24
Issue number10
DOIs
Publication statusPublished - Jun 19 2010

Keywords

  • immune reconstitution
  • immunological-nonresponders
  • T-cell function
  • T-cell maturation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Marchetti, G., Gazzola, L., Trabattoni, D., Bai, F., Ancona, G., Ferraris, L., Meroni, L., Galli, M., Clerici, M., Gori, A., & D'Arminio Monforte, A. (2010). Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART. AIDS (London, England), 24(10), 1455-1460. https://doi.org/10.1097/QAD.0b013e328339cf40