title: Poor immune reconstitution in HIV-infected patients associates with high percentage of regulatory CD4+ T cells.
abstract: CD4(+) regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4(+) T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4(+) T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4(+) T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4(+) T cells) had the worse CD4(+) T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4(+) T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4(+) T cell recovery among immunological non-responder HIV(+) individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4(+) T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation.
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
authors: Ana
authors: A
authors: Horta
authors: Claudia
authors: C
authors: Nobrega
authors: Pedro
authors: P
authors: Amorim-Machado
authors: Vitor
authors: V
authors: Coutinho-Teixeira
authors: Palmira
authors: P
authors: Barreira-Silva
authors: Susana
authors: S
authors: Boavida
authors: Patrício
authors: P
authors: Costa
authors: Rui
authors: R
authors: Sarmento-Castro
authors: António Gil
authors: AG
authors: Castro
authors: Margarida
authors: M
authors: Correia-Neves
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000821:virology; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD