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

Marchetti, Giuliaa; Gazzola, Lidiaa; Trabattoni, Dariab; Bai, Francescaa; Ancona, Giuseppea; Ferraris, Laurenziac; Meroni, Lucac; Galli, Massimoc; Clerici, Mariod; Gori, Andreae; d'Arminio Monforte, Antonellaa

doi: 10.1097/QAD.0b013e328339cf40
Basic Science: Concise Communications

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.

aDepartment of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, ‘San Paolo’ Hospital, University of Milan, Italy

bChair of Immunology DISP, LITA VIALBA, Italy

cDepartment of Clinical Sciences, Chair of Infectious Diseases and Tropical Medicine, ‘Luigi Sacco’ Hospital, University of Milan, Italy

dDepartment of Biomedical Sciences and Technology, University of Milan, and Don C. Gnocchi Foundation, IRCCS, Milan, Italy

eDivision of Infectious Diseases, ‘San Gerardo’ Hospital, Monza, Italy.

Received 7 December, 2009

Revised 9 March, 2010

Accepted 15 March, 2010

Correspondence to Giulia Marchetti, MD, PhD, Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, ‘San Paolo’ Hospital, University of Milan, via A. di Rudinì 8, 20142 Milan, Italy. Tel: +39 02 81843064; fax: +39 02 81843054; e-mail: giulia.marchetti@unimi.it

© 2010 Lippincott Williams & Wilkins, Inc.