Loss of Dmrta1 alters CD8+ T cell activation and resistance to influenza virus infection.

The generation and function of effector and memory CD8+ T cells are crucial for effective immune responses and long-term immunity. Using gene expression analysis, we found that doublesex- and mab-3-related transcription factor like family A1 (Dmrta1), a member of the DMRT family of transcription factors, is highly expressed in activated and memory CD8+ T cells. In this study, we investigated the role of Dmrta1 in the activation and differentiation of CD8+ T cells. The Dmrta1-deficient (Dmrta1-KO) mice showed an equivalent number of thymic and splenic T cells compared with wild-type mice. Dmrta1 deficiency in T cells resulted in impaired early activation of CD8+ but not CD4+ T cells and reduced expression of granzyme B in CD8+ T cells following influenza virus infection. Although virus-specific CD8+ T cell numbers and cytotoxicity in the lung were comparable between wild-type and Dmrta1-deficient mice during primary infection, Dmrta1-KO mice exhibited a transient accumulation of virus-specific CD8+ T cells in the spleen with reduced cytotoxic activity. Upon secondary challenge, memory CD8+ T cells from Dmrta1-KO mice showed persistent defects in granzyme B expression and cytotoxic function. These findings demonstrate that Dmrta1 modulates the early activation of naïve CD8+ T cells and supports the cytotoxic functionality of both effector and memory CD8+ T cells, particularly in secondary lymphoid organs, with significant implications for antiviral immunity.