AUTHOR=Pavelko Kevin D. , Bell Michael P. , Harrington Susan M. , Dong Haidong TITLE=B7-H1 Influences the Accumulation of Virus-Specific Tissue Resident Memory T Cells in the Central Nervous System JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01532 DOI=10.3389/fimmu.2017.01532 ISSN=1664-3224 ABSTRACT=

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.