The relationship between IL-7Rα polymorphisms and MAIT cell dysfunction in treated HIV-1 infection — ASN Events
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  3. The relationship between IL-7Rα polymorphisms and MAIT cell dysfunction in treated HIV-1 infection

The relationship between IL-7Rα polymorphisms and MAIT cell dysfunction in treated HIV-1 infection (#77)

Muhammad Yaaseen Gulam 1 , Noor Kamila Abdullah 2 , Adeeba Kamarulzaman 2 , Sharon R. Lewin 3 4 , Johan K. Sandberg 5 , Reena Rajasuriar 2 3 , Edwin Leeansyah 1 5
  1. Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore
  2. Centre of Excellence for Research in AIDS (CERIA), University of Malaya, Kuala Lumpur, Malaysia
  3. Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia
  4. Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia
  5. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

MAIT cells were persistently depleted and functionally exhausted in HIV-infected patients despite long-term antiretroviral therapy (ART). Furthermore, we have shown that IL-7 could rescue functionality in MAIT cells from HIV-infected patients in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7 receptor α-subunit (IL-7Rα/CD127), which modulate soluble(s)IL-7Rα levels, influence bioavailability of circulating IL-7 and affect subsequent downstream signalling. Given the strong effects of IL-7 on MAIT cells, we therefore investigated the potential role of IL-7Rα polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected patients on long-term ART.

The IL-7Rα promoter haplotypes were identified by haplotype-tagging SNPs from a cohort of 22 HC and 36 HIV-1-infected patients. The number and phenotype of MAIT cells, levels of the MAIT cell classical transcription factors (TFs), and MAIT cell function following bacterial stimulation were measured by flow cytometry.

We found MAIT cell levels and functions in infected patients were still significantly lower than those of HC despite an average of 7 years on suppressive ART. Interestingly, HC with IL-7Rα haplotype 2, defined as T-allele carriers at the tagging SNP rs6897932, had higher levels of MAIT cells in circulation than HC with non-haplotype 2 polymorphisms.  These MAIT cells also expressed higher levels of classical TFs and appeared to have better functionality. sIL-7Rα levels were lower in HC harbouring haplotype 2, and there was a trend towards an inverse correlation between sIL-7Rα levels and MAIT cell frequency. These associations were not observed in HIV-infected patients, despite sIL-7Rα levels were still significantly lower in haplotype 2 patients. Notably, there was a significant correlation between MAIT cell levels and ART duration that was observed only in patients harbouring IL-7Rα haplotype 2. These results indicate that IL-7Rα polymorphism may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection.