Poster Presentation The Australasian Society for Immunology 2017 Annual Scientific Meeting

Patients who succumb to H7N9 infection have impaired CD8⁺ T-cell function. Our laboratory has previously shown that expression of the activation markers, CD38 and HLA-DR increased on CD8⁺ T cells during early stages of infection, and then gradually declined during the recovery. Conversely, patients with fatal disease outcomes displayed high and prolonged expression of CD38⁺HLA-DR⁺ on CD8⁺ T cells. In order to understand whether the CD38⁺HLA-DR⁺ CD8⁺ T cells are activated in virus-specific (via T cell receptor; TCR) or non-virus-specific (via inflammation) manners in flu infection, human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with an influenza-derived M1_58-66 peptide at varying concentrations and conditions. We found that CD38⁺HLA-DR⁺ upregulation occurred 8 days after peptide stimulation. However, not all CD38⁺HLA-DR⁺ CD8⁺ T cells were specific for the M1_58-66 peptide, indicating that there are indeed other ways to trigger CD38⁺HLA-DR⁺ expression on CD8⁺ T cells. In addition, M1_58-66⁺ CD8⁺ T cells after high dose peptide stimulation rarely expressed IFN-γ in contrast to low dose peptide stimulation. Using an in vivo approach of influenza infection in mice, we also demonstrated a higher proportion of CD38⁺MHCII⁺ CD8⁺ T cells within both D^bNP₃₆₆ tetramer-positive and -negative populations after high dose infection than that with low dose influenza virus infection. This suggests that some CD8⁺ T cells can become activated in a non-virus manner to express CD38⁺MHCII⁺, which is consistent with our in vitro peptide stimulation data. Thus, our study illustrates that CD38⁺HLA-DR⁺ CD8⁺ T cells can be activated in both virus-specific and non-virus specific manners, and this CD8⁺ T-cell subset might represent a potential biomarker for dysfunctional immune responses.