MAIT Cell Loss and Reconstitution in HIV-1 Disease

Han, Fei; Zheng, Yi-Chao; Ho, Amanda; Ma, Shaoping; Sandberg, Johan K.; Leeansyah, Edwin

doi:10.1615/critrevimmunol.2022042906

Cited by 6 publications

(6 citation statements)

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“…The frequency and function of MAIT cells are impaired in chronic untreated HIV-1-infected patients and do not fully recover following long-term cART ( 19 , 22 , 25 ). In agreement with previous studies ( 19 , 22 , 58 ), circulating MAIT cell levels from HIV-1-infected individuals with long-term cART ( Supplementary Table 4 ) were still significantly lower than those from uninfected adult males from the same HC cohort ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

“…However, during the first weeks of HIV-1 infection, absolute counts of intestinal and circulating MAIT cells are elevated, indicating the proliferation of MAIT cells at the early phase of acute HIV-1 infection (24,26). Various mechanisms of MAIT cell loss during chronic HIV-1 infection were recently reviewed by Han et al (25), including cytokine dysregulation (27), persistent activation by microbial metabolites from microbial translocation (28,29), MAIT cell death due to apoptosis and pyroptosis (30), and homing to inflamed tissues (23,25). Unfortunately, combination antiretroviral therapy (cART) is ineffective in restoring the circulating MAIT cell pool (19,24).…”

Section: Introductionmentioning

confidence: 99%

“…We and others have reported the loss of MAIT cells in circulation during chronic HIV-1 infection ( 19 , 22 – 24 ). Residual MAIT cells from chronically HIV-1-infected patients are highly activated and show functional impairment in response to Escherichia coli stimulation ( 19 , 23 , 25 ). However, during the first weeks of HIV-1 infection, absolute counts of intestinal and circulating MAIT cells are elevated, indicating the proliferation of MAIT cells at the early phase of acute HIV-1 infection ( 24 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

“…Various mechanisms of MAIT cell loss during chronic HIV-1 infection were recently reviewed by Han et al. ( 25 ), including cytokine dysregulation ( 27 ), persistent activation by microbial metabolites from microbial translocation ( 28 , 29 ), MAIT cell death due to apoptosis and pyroptosis ( 30 ), and homing to inflamed tissues ( 23 , 25 ). Unfortunately, combination antiretroviral therapy (cART) is ineffective in restoring the circulating MAIT cell pool ( 19 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

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IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection

et al. 2022

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MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection

et al. 2022

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“…MAIT cells respond to viral infections through MR1‐independent and cytokine‐dependent pathways 5 . However, whether MAIT cells can directly eliminate HBV infection remains unclear.…”

Section: Figurementioning

confidence: 99%