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

• Published in: European journal of clinical microbiology & infectious diseases Vol. 34; no. 2; pp. 267 - 275
• Main Authors: Vallejo, A., Abad-Fernández, M., Moreno, S., Moreno, A., Pérez-Elías, M. J., Dronda, F., Casado, J. L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2015
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - immunology; Cross-Sectional Studies; CTLA-4 Antigen - metabolism; Female; HIV Infections - complications; HIV Infections - immunology; HIV-1 - immunology; Humans; Internal Medicine; Leishmania - immunology; Leishmaniasis, Visceral - complications; Leishmaniasis, Visceral - immunology; Male; Medical Microbiology; Middle Aged; Receptors, CCR5 - metabolism; T-Lymphocytes, Regulatory - immunology; Cutaneous Leishmaniasis; Leishmaniasis; Maraviroc; Visceral Leishmaniasis; Treg Cell
• ISSN: 0934-9723; 1435-4373
• DOI: 10.1007/s10096-014-2229-1

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.