Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals.
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.
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Denmark.|Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Denmark.
Hans Jakob
HJ
Hartling
Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Denmark.
Lars P
LP
Ryder
Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Denmark.
Henrik
H
Ullum
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Niels
N
Ødum
Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Denmark.
Susanne Dam
SD
Nielsen
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000378:metabolism*; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain