High levels of CD4⁺ CTLA-4⁺ Treg cells and CCR5 density in HIV-1-infected patients with visceral leishmaniasis

Eur J Clin Microbiol Infect Dis. 2015 Feb;34(2):267-75. doi: 10.1007/s10096-014-2229-1. Epub 2014 Aug 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen / metabolism*
  • Cross-Sectional Studies
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Leishmania / immunology*
  • Leishmaniasis, Visceral / complications
  • Leishmaniasis, Visceral / immunology*
  • Male
  • Middle Aged
  • Receptors, CCR5 / metabolism*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CCR5 protein, human
  • CTLA-4 Antigen
  • Receptors, CCR5