B7-H1 Influences the Accumulation of Virus-Specific Tissue Resident Memory T Cells in the Central Nervous System

Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment, yet precise knowledge of how this pathway provides benefit continues to evolve. Here, we report a novel role for the immune checkpoint ligand B7-H1 in the accumulation of tissue-resident memory CD8(+) T-cells (T(RM)). After intracranial infection, Theiler’s murine encephalomyelitis virus (TMEV) generates T(RM) that are maintained in the central nervous system (CNS) tissues of B7-H1(WT) animals. Although no differences in acute T-cell responses between B7-H1(WT) and B7-H1(KO) are observed, at long-term periods post-infection the maintenance of CD8(+) T(RM) is diminished in B7-H1(KO) animals. This is accompanied by redistribution of the resident CD8(+) population from primarily CD103(+) T(RM) to a diminished population of T(RM) and a preponderance of non-specified PD-1(+) CD103(−) CD8(+) T-cells. T-cell transfer studies demonstrate that host B7-H1 is necessary for maintaining T(RM) and limiting accumulation of PD-1(+) CD103(−) CD8(+) T-cells. The lack of host B7-H1 results in compromised control of a heterologous virus re-challenge demonstrating a functional defect in T(RM) mediated virus control. This study reveals a new role for B7-H1 in T(RM) and pro-inflammatory PD-1(+) CD103(−) CD8(+) T-cell accumulation in the CNS and gives insight for using B7-H1/PD-1 blockade in modulating long-term T-cell protection.