Mucosal-associated invariant T (MAIT) cells help combat opportunistic infections. Thus, MAIT cells are of interest in HIV/SIV vaccination and infection. We investigated MAIT cell dynamics and function in rhesus macaque blood and bronchoalveolar lavage (BAL) following mucosal adenovirus (Ad)-SIV recombinant priming, intramuscular SIV envelope boosting and infection following repeated low-dose intravaginal SIV exposures. Increased frequencies of blood MAIT cells over the course of vaccination were observed, which were maintained even 12-weeks post-SIV infection. BAL MAIT cells only increased after the first Ad immunization. Vaccination increased MAIT cell levels in blood and BAL expressing the antiviral cytokine IFN-γ and TNF-α and the proliferation marker Ki67. Upon T cell-specific α-CD3, α-CD28 stimulation, MAIT cells showed a greater capacity to secrete cytokines/chemokines associated with help for B cell activation, migration and regulation compared to CD3+MR1− cells. Culture of MAIT cell supernatants with B cells led to greater tissue like memory B cell frequencies. MAIT cell frequencies in blood and BAL correlated with SIV-specific antibody levels in rectal secretions and with SIV-specific tissue resident memory B cells. Overall, SIV vaccination influenced MAIT cell frequency and functionality. The potential for MAIT cells to provide help to B cells was evident during both vaccination and infection.
NK cells are essential for controlling viral infections. We investigated NK cell and innate lymphoid cell (ILC) dynamics and function in rhesus macaque rectal tissue and blood following mucosal priming with replicating adenovirus (Ad)-SIV recombinants, systemic boosting with SIV envelope protein, and subsequent repeated low-dose intravaginal SIV exposures. Mucosal memory-like NK and ILC subsets in rectal and vaginal tissues of chronically infected macaques were also evaluated. No differences in NK cell or ILC frequencies or cytokine production were seen between vaccinated and Ad-empty/alum controls, suggesting responses were due to the Ad-vector and alum vaccine components. Mucosal NKp44 + ILCs increased postvaccination and returned to prelevels postinfection. The vaccine regimen induced mucosal SIV-specific Ab, which mediated Ab-dependent cellular cytotoxicity and was correlated with mucosal NKp44 + CD16 + ILCs. Postvaccination NKp44 + and NKp44 + IL-17 + ILC frequencies were associated with delayed SIV acquisition and decreased viremia. In chronically SIV-infected animals, NKp44 + ILCs negatively correlated with viral load, further suggesting a protective effect, whereas, NKG2A 2 NKp44 2 double-negative ILCs positively correlated with viral load, indicating a pathogenic role. No such associations of circulating NK cells were seen. Dg NK cells in mucosal tissues of chronically infected animals exhibited impaired cytokine production compared with non-Dg NK cells but responded to anti-gp120 Ab and Gag peptides, whereas non-Dg NK cells did not. Mucosal Dg NKp44 + and Dg DN cells were similarly associated with protection and disease progression, respectively. Thus, the data suggest NKp44 + ILCs and Dg cells contribute to SIV infection outcomes. Vaccines that promote mucosal NKp44 + and suppress double-negative ILCs are likely desirable.
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