Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART.
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-gamma-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/microl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4(+) > 500 cells/microl, HIV-RNA < 50 copies/ml).


RESULTS
We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RA(-)CCR7(-) CD4(+)/CD8(+) and Th2-committed CD7(-)CD4(+), 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.


CONCLUSIONS
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.
Marchetti
Giulia
G
Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, San Paolo Hospital, University of Milan, Milan, Italy. giulia.marchetti@unimi.it
Gazzola
Lidia
L
Trabattoni
Daria
D
Bai
Francesca
F
Ancona
Giuseppe
G
Ferraris
Laurenzia
L
Meroni
Luca
L
Galli
Massimo
M
Clerici
Mario
M
Gori
Andrea
A
D'Arminio Monforte
Antonella
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003430:Cross-Sectional Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged
D007376:Interleukin-2; D007371:Interferon-gamma