The generation of CD8+CD103+ tissue resident memory cells is decreased in the brain of B7-H1 knockouts after virus infection

Abstract

Abstract The generation of CD8+ tissue resident memory T-cells (TRM) ensures rapid recognition of viruses after secondary infection and is important for long term defense against tumor formation. We find that intracranial infection with Theiler’s murine encephalomyelitis virus (TMEV) generates a robust CD8+ effector response after acute infection. This response resolves with virus clearance and only CD8+CD103+ brain TRM remain. Much is known about the development of acute T-cell responses to TMEV, however less is known about how TRM are generated and maintained within the brain. Previously, we found that B7-H1 prevents the entry of effector CD8+ T-cells into the memory pool. In the current studies we explore the role of B7-H1 in the development and maintenance of brain TRM. We find that B7-H1 expression within the host tissues is important for maintaining TRM in the brain after TMEV infection. By studying acute and long-term post-infected B7-H1 knockout and wild-type mice we find that B7-H1 contributes to the formation and maintenance of TRM. The expression of B7-H1 is required within the host tissues to promote this memory population as the absence of B7-H1 on T-cells did not alter TRM formation. In addition, we find an increase in CD103 negative antigen non-specific CD8+ PD1+ T-cells in B7-H1 knockout hosts, a population previously identified as CD8+ regulatory T cells. This suggests that B7-H1 may also control this population of tissue resident CD8+ regulatory T cells (TRR). These findings will be important for further understanding the PD1/B7-H1 axis and its role in TRM and TRR development and for understanding how therapies that target these molecules can be optimized to promote T-cell memory formation and maintenance when used as therapy.