Background
HIV-2 is characterised by more indolent clinical progression than HIV-1, including decreased T-cell activation and limited immune exhaustion. However, it remains unclear how HIV subtypes impact the unconventional lymphocyte compartment, including mucosal-associated invariant T-cells (MAIT), invariant natural killer T-cells (iNKT), and Vδ2+ T-cells which mediate gut barrier defence and mucosal inflammation. To investigate whether the distinct clinical courses of HIV subtypes are associated with altered frequency and function of unconventional lymphocytes, we assessed mitochondrial and exhaustion profiles of these populations in HIV-1, HIV-2, and healthy controls (HC).
Methods
PBMCs from people with HIV-1 (n=6) people with HIV-2 (n=6) and HC (n=6) were analysed by 26 colour flow cytometry. In addition to conventional T-cell lineage markers, iNKT, MAIT, and Vδ2+ subsets were assessed for frequency and expression of exhaustion markers (PD1, TIGIT) and mitochondrial function (MTG, TMRM).
Results
Both HIV-1 and HIV-2 cohorts were virally suppressed (VL<50 c/mL) and on ART (clinical demographics summarised in Table 1). iNKT frequency did not differ between cohorts (p=0.6). HIV-1 was associated with increased MAIT cell frequency (p=<0.03) and expression of TIGIT (p=<0.02) relative to HIV-2, although mitochondrial profile of MAIT cells was comparable between HIV cohorts (p=0.4). Circulating Vδ2+ frequency was higher (p=<0.03) in HIV-1 than in HIV-2, but mitochondrial activity was markedly higher (p=<0.03) in HIV-2 relative to HIV-1 and HC.
Conclusions
Preliminary analysis suggests that MAIT and Vδ2+ T-cell frequencies are higher in HIV-1 than in HIV-2, but there is a higher proportion of functional mitochondria in MAIT cells in HIV-2. These data suggest that the innate lymphocyte pool is differentially impacted by HIV subtypes, which may influence gut reservoir size and clinical course of infection. Future work will focus on gut homing potential and add additional markers of mitochondrial function including mtDNA copy number, ROS generation, and cellular respiration.
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