Human MAIT cells sit at the interface between innate and adaptive immunity, are polyfunctional and are capable of killing pathogen infected cells via recognition of the Class IB molecule MR1. MAIT cells have recently been shown to possess an antiviral protective role in vivo and we therefore sought to explore this in relation to HIV-1 infection. There was marked activation of MAIT cells in vivo in HIV-1 infected individuals, which decreased following ART. Stimulation of THP1 monocytes with R5 tropic HIVBAL potently activated MAIT cells in vitro. This activation was dependent on IL-12 and IL-18 but was independent of the TCR. Upon activation, MAIT cells were able to up-regulate granzyme B, IFNg and HIV-1 restriction factors CCL3, 4 and 5. Restriction factors produced by MAIT cells inhibited HIV-1 infection of primary PBMCs and immortalized target cells in vitro. These data reveal MAIT cells to be an additional T cell population responding to HIV-1, with a potentially important role in controlling viral replication at mucosal sites.
Raw data from main figures are provided as source data files.
- Paul Klenerman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The SPARTAC trial (EudraCT Number: 2004-000446-20) was approved by the following authorities: the Medicines and Healthcare products Regulatory Agency (UK), the Ministry of Health (Brazil), the Irish Medicines Board (Ireland), the Medicines Control Council (South Africa) and the Uganda National Council for Science and Technology (Uganda). It was also approved by the following ethics committees in the participating countries: the Central London Research Ethics Committee (UK), Hospital Universitário Clementino Fraga Filho Ethics in Research Committee (Brazil), the Clinical Research and Ethics Committee of Hospital Clinic in the province of Barcelona (Spain), the Adelaide and Meath Hospital Research Ethics Committee (Ireland), the University of Witwatersrand Human Research Ethics Committee, the University of Kwazulu-Natal Research Ethics Committee and the University of Cape Town Research Ethics Committee (South Africa), Uganda Virus Research Institute Science and ethics committee (Uganda), the Prince Charles Hospital Human Research Ethics Committee and St Vincent's Hospital Human Research Ethics Committee (Australia) and the National Institute for Infectious Diseases Lazzaro Spallanzani, Institute Hospital and the Medical Research Ethics Committee, and the ethical committee of the Central Foundation of San Raffaele, MonteTabor (Italy).Recruitment for and studies within the HEATHER cohort were approved by the West Midlands-South Birmingham Research Ethics Committee (reference 14/WM/1104). Recruitment of CHI participants were approved by The University of the Free State Ethics Committee (ETOVS 171/08). LTNPs recruitment was approved by The St Vincent's Human Research Ethics Committee (EC00140) approval number: HREC/12/SVH/298, SVH 12/217. PBMCs obtained from healthy donors were approved by the Sheffield Research Ethics Committee (reference 16/YH/0247). Participants were aged 18 years or older, all participants from each of the above mentioned cohorts gave informed and written consent for their participation in these studies.
- Stipan Jonjic, University of Rijeka, Croatia
© 2021, Phetsouphanh et al.
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