MicroRNA-139 Expression Is Dispensable for the Generation of Influenza-Specific CD8⁺ T Cell Responses

MicroRNAs (miRNAs/miRs) are small, endogenous noncoding RNAs that are important post-transcriptional regulators with clear roles in the development of the immune system and immune responses. Using miRNA microarray profiling, we characterized the expression profile of naive and in vivo generated murine effector antiviral CD8⁺ T cells. We observed that out of 362 measurable mature miRNAs, 120 were differentially expressed by at least 2-fold in influenza-specific effector CD8⁺ CTLs compared with naive CD8⁺ T cells. One miRNA found to be highly downregulated on both strands in effector CTLs was miR-139. Because previous studies have indicated a role for miR-139-mediated regulation of CTL effector responses, we hypothesized that deletion of miR-139 would enhance antiviral CTL responses during influenza virus infection. We generated miR-139^-/- mice or overexpressed miR-139 in T cells to assess the functional contribution of miR-139 expression in CD8⁺ T cell responses. Our study demonstrates that the development of naive T cells and generation or differentiation of effector or memory CD8⁺ T cell responses to influenza virus infection are not impacted by miR-139 deficiency or overexpression; yet, miR-139^-/- CD8⁺ T cells are outcompeted by wild-type CD8⁺ T cells in a competition setting and demonstrate reduced responses to Listeria monocytogenes Using an in vitro model of T cell exhaustion, we confirmed that miR-139 expression similarly does not impact the development of T cell exhaustion. We conclude that despite significant downregulation of miR-139 following in vivo and in vitro activation, miR-139 expression is dispensable for influenza-specific CTL responses.