Cognate epitope is dispensable in maintenance of PD-1 expression on tissue-resident CD8+ cells

• Published in: The Journal of immunology (1950) Vol. 198; no. 1_Supplement; pp. 78 - 78.6
• Main Authors: Shwetank, Frost, Elizabeth L., Abdelsamed, Hossam Aly, Mockus, Taryn, Maru, Saumya, Youngblood, Ben A, Lukacher, Aron
• Format: Journal Article
• Language: English
• Published: 01-05-2017
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.198.Supp.78.6

Persistent CNS infection by mouse polyomavirus (MuPyV) establishes a tissue-resident memory (TRM) CD8+ T cell population possessing higher TCR affinity than the memory cells in spleen. This necessitates a mechanism to regulate the functions of a non-replenished TRM population. Here, we report that virus-specific CD8+ T cells express PD-1 during acute infection and remain PD-1hion brain-infiltrating T cells. In contrast, antiviral memory CD8+ T cells in the spleen downregulate PD-1 expression during persistent infection, despite having similar viral load as the brain. The Pdcd1 promoter was found to be partially remethylated following its downregulation in the splenic population while the locus remained unmethylated in the brain-resident cells. Antiviral TRM cells purified from infected brain when transferred into a naïve mouse via intracerebral route, remained PD-1hi. Thus, epitope as well as inflammation are dispensable for maintenance of PD-1 expression. Absence of PD-1 signaling in an in vitro peptide stimulation assay resulted in augmented IFN-γ production and in vivo absence of PD-1 or PD-L1 resulted in increased IFN-γ-dependent microglial activation, indicating that PD-1 operates to limit CD8+ T cell-dependent neuroinflammation. PD-L1 was found to be expressed on infiltrating myeloid cells and astrocytes; astrocytes were also found to support productive MuPyV infection. PD-L1−/− mice had fewer anti-MuPyV brain-TRM cells, but increased proportion of the cells that were CD103hi, an αE integrin expressed by TRM cells. In summary, our data shows that PD-1 plays an important role in maintenance of antiviral CD8+ TRM cells in the brain and its expression is independent of the cognate epitope.