title: High levels of CD4⁺ CTLA-4⁺ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis.
abstract: Visceral leishmaniasis (VL) in HIV-1-infected patients has been associated with poor immunological recovery and frequent disease relapses. The aim of this study was to analyse the role of T cell populations, Treg cells and CCR5 density in patients with VL compared to HIV-1-infected patients without leishmaniasis. A cross-sectional study of nine Leishmania-HIV-1-coinfected (LH) patients with VL receiving suppressive cART for at least 1 year were compared to 16 HIV-1-infected patients with non-immunological response (NIR, CD4 count below 250 cells/mm(3)) and 26 HIV-1-infected patients with immunological response (IR, CD4 count above 500 cells/mm(3)) without leishmaniasis. LH patients had a deep depletion of naïve T cells (p = 0.002), despite similar levels of effector T cells compared to NIR patients. CD4 Treg cells were similar compared to NIR patients, but higher compared to IR patients (p < 0.001). Interestingly, CD4 Treg CTLA-4(+) cells were higher in LH patients compared to either NIR or IR patients (p = 0.022 and p < 0.001, respectively), and the CD4 Treg/TEM ratio was similar to NIR patients, but higher compared to IR patients (p = 0.017). CCR5(+) T cell levels were higher compared to IR patients (p < 0.001), while CCR5 density on T cells were higher compared to both NIR and IR patients (p < 0.005 in both cases). Higher levels of CD4(+) CTLA-4(+) Treg cells and CCR5 density on CD8(+) T cells are strongly associated with VL in HIV-1-infected patients. Also, these patients have a poor immunological profile that might explain the persistence and relapse of the pathogen.
authors.affiliation: Department of Infectious Diseases, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University Hospital Ramón y Cajal, Ctra Colmenar Km 9, 28034, Madrid, Spain, alejandro.vallejo@salud.madrid.org.
authors.forename: A
authors.initials: A
authors.lastname: Vallejo
authors.forename: M
authors.initials: M
authors.lastname: Abad-Fernández
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: M J
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: F
authors.initials: F
authors.lastname: Dronda
authors.forename: J L
authors.initials: JL
authors.lastname: Casado
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007891:Leishmania / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000150:complications / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C584933:CCR5 protein, human; D060908:CTLA-4 Antigen; D019713:Receptors, CCR5