Gene variation in IL-7 receptor (IL-7R)[alpha] affects IL-7R response in CD4+ T cells in HIV-infected individuals

• Published in: Scientific reports Vol. 7; p. 42036
• Main Authors: Hartling, Hans Jakob, Ryder, Lars P, Ullum, Henrik, Ødum, Niels, Nielsen, Susanne Dam
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.02.2017
• Subjects: Antiretroviral drugs; CD4 antigen; HIV; Human immunodeficiency virus; Immunology; Infections; Lymphocytes; Lymphocytes T; Signal transduction
• ISSN: 2045-2322
• DOI: 10.1038/srep42036

Optimal CD4+ T cell recovery after initiating combination antiretroviral treatment (cART) in HIV infection reduces risk of morbidity and mortality. T-allele homozygosity ('TT') in the single nucleotide polymorphism, rs6897932(C/T), in the IL-7 receptor α (IL-7RA) is associated with faster CD4+ T cell recovery after cART initiation compared to C-allele homozygosity in rs6897932 ('CC'). However, underlying mechanisms are unknown. We aimed to examine potential mechanisms explaining the association between rs6897932 and CD4+ T cell recovery. Ten 'TT' and 10 'CC' HIV-infected individuals matched on gender, age, and nadir and current CD4+ T cell counts were included in a cross-sectional study. 'TT' individuals had higher proportion of CD4+ T cells expressing pSTAT5 compared to 'CC' individuals after stimulating with IL-7, especially when co-stimulated with soluble IL7-RA (sIL-7RA). Furthermore, 'TT' individuals had a higher proportion of proliferating CD4+ T cells after 7 days of culture with IL-7 + sIL-7RA compared to 'CC' individuals. No differences between 'TT' and 'CC' in binding of biotinylated IL-7 were found. In conclusion, increased signal transduction and proliferation in response to IL-7 was found in 'TT' compared to 'CC' HIV-infected individuals providing a mechanistic explanation of the effect of rs6897932 T-allele on CD4+ T cell recovery in HIV infection.