Methionine enkephalin(MENK) upregulated memory T cells in anti-influenza response.

Novel prophylactic drugs and vaccination strategies for protection against influenza virus should induce specific effector T-cell immune responses in pulmonary airways and peripheral lymphoid organs. Designing approaches that promote T-cell-mediated responses and memory T-cell differentiation would strengthen host resistance to respiratory infectious diseases. The results of this study showed that pulmonary delivery of MENK via intranasal administration reduced viral titres, upregulated opioid receptor MOR and DOR, increased the proportions of T-cell subsets including CD8⁺ T cells, CD8⁺ T_EM cells, NP/PA-effector CD8⁺ T_EM cells in bronchoalveolar lavage fluid and lungs, and CD4⁺/CD8⁺ T_CM cells in lymph nodes to protect mice against influenza viral challenge. Furthermore, we demonstrated that, on the 10th day of infection, the proportions of CD4⁺ T_M and CD8⁺ T_M cells were significantly increased, which meant that a stable T_CM and T_EM lineage was established in the early stage of influenza infection. Collectively, our data suggested that MENK administered intranasally, similar to the route of natural infection by influenza A virus, could exert antiviral activity through upregulating T-cell-mediated adaptive immune responses against influenza virus.