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

Kevin D. Pavelko, Michael P. Bell, Susan M. Harrington, Haidong Dong

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 (TRM). After intracranial infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM 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(+) TRM is diminished in B7-H1(KO) animals. This is accompanied by redistribution of the resident CD8(+) population from primarily CD103(+) TRM to a diminished population of TRM 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 TRM 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 TRM mediated virus control. This study reveals a new role for B7-H1 in TRM 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.