title: Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses.
abstract: Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (<50%) to high (>50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of>50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Macal
authors.forename: S
authors.initials: S
authors.lastname: Sankaran
authors.forename: T-W
authors.initials: TW
authors.lastname: Chun
authors.forename: E
authors.initials: E
authors.lastname: Reay
authors.forename: J
authors.initials: J
authors.lastname: Flamm
authors.forename: T J
authors.initials: TJ
authors.lastname: Prindiville
authors.forename: S
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014779:Virus Replication
chemical_list: D020381:Interleukin-17