Progressive Simian-Human Immunodeficiency Virus (SHIV) infection alters expression of key surface and transcriptional proteins on macaque MAIT cells — ASN Events
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  3. Progressive Simian-Human Immunodeficiency Virus (SHIV) infection alters expression of key surface and transcriptional proteins on macaque MAIT cells

Progressive Simian-Human Immunodeficiency Virus (SHIV) infection alters expression of key surface and transcriptional proteins on macaque MAIT cells (#82)

Jennifer A Juno 1 , Sidonia Eckle 1 , Kathleen Wragg 1 , Bronwyn Meehan 1 , Thakshila Haripriya Amarasena 1 , Jeffrey Mak 2 , Ligong Liu 2 , David Fairlie 2 , James McCluskey 1 , Stephen J Kent 1
  1. University of Melbourne, Melbourne, VIC, Australia
  2. Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia

Background: MR1-restricted T cells (or MAIT cells) are depleted from the peripheral blood and exhibit functional defects during HIV infection. The mechanisms responsible for this depletion and the significance of MAIT cell dysfunction during HIV infection are not fully understood. To address this gap in knowledge in a relevant animal model, we produced Macaca nemestrina-specific, 5-OP-RU-loaded MR1 tetramers to identify pigtail macaque (PTM) MAIT cells and to characterize their phenotype and function in naïve and SHIV-infected macaques.

Results: MAIT cells were readily identified in PTM PBMC and share many phenotypic similarities with human MAIT cells, including expression of the Vα7.2 TCR, CCR6, IL-18Ra, CCR5, CXCR3 and the transcription factors PLZF and Eomes, although they express relatively low levels of Tbet. PTM MAITs exhibit robust expression of IFNγ, TNFα, GM-CSF and IL-17 following PMA/Io stimulation, but their ex vivo responses to direct 5-OP-RU stimulation are substantially weaker than human MAIT cells. Following SHIV challenge, PTM MAIT frequency is relatively stable for as long as 52 weeks post-infection and does not decline in a manner analogous to that observed in HIV infection. Progressive SHIV infection is, however, associated with phenotypic perturbation of MAIT cells, including rapid loss of CXCR3 expression, decreased CCR5 surface density, and loss of PLZF expression. Interestingly, while the majority of conventional T cells expressing the mucosal homing marker and HIV/SIV binding protein α4β7 are depleted during SHIV infection, MAIT cell a4b7 expression is maintained.

Conclusions: The production of M. nemestrina-specific MR1 tetramers has allowed for the identification and characterization of MAIT cells in PTMs for the first time. The lack of MAIT cell depletion during progressive SHIV infection is notably distinct from human HIV infection, and differences in macaque and human α4β7 expression and functional profile may point to mechanisms underpinning the HIV-specific depletion of these cells.