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

Abstract

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.