Abstract
Objectives:
Although co-expression of CD38 and HLA-DR reflects T-cell activation during viral infections, high and prolonged CD38+HLA-DR+ expression is associated with severe disease. To date, the mechanism underpinning expression of CD38+HLA-DR+ is poorly understood.
Methods:
We used mouse models of influenza A/H9N2, A/H7N9 and A/H3N2 infection to investigate mechanisms underpinning CD38+MHC-II+ phenotype on CD8+ T cells. To further understand MHC-II trogocytosis on murine CD8+ T cells as well as the significance behind the scenario, we used adoptively transferred transgenic OT-I CD8+ T cells and A/H3N2-SIINKEKL infection.
Results:
Analysis of influenza-specific immunodominant DbNP366 +CD8+ T-cell responses showed that CD38+MHC-II+ co-expression was detected on both virus-specific and bystander CD8+ T cells, with increased numbers of both CD38+MHC-II+CD8+ T-cell populations observed in immune organs including the site of infection during severe viral challenge. OT-I cells adoptively transferred into MHC-II-/- mice had no MHC-II after infection, suggesting that MHC-II was acquired via trogocytosis. The detection of CD19 on CD38+MHC-II+ OT-I cells supports the proposition that MHC-II was acquired by trogocytosis sourced from B cells. Co-expression of CD38+MHC-II+ on CD8+ T cells was needed for optimal recall following secondary infection.
Conclusions:
Overall, our study demonstrates that both virus-specific and bystander CD38+MHC-II+ CD8+ T cells are recruited to the site of infection during severe disease, and that MHC-II presence occurs via trogocytosis from antigen-presenting cells. Our findings highlight the importance of the CD38+MHC-II+ phenotype for CD8+ T-cell recall.