T cell surveillance of the CNS
Phenotyping T cells in human post mortem brain
Joost Smolders, MD, PhD
The central nervous system (CNS) is a structurally and functionally unique yet vulnerable organ that requires efficient immune protection against viral infections. It has become clear that most tissues are populated by tissue-resident memory T cells (TRM), which are adapted to their niche and appear to be indispensable for local protection against infection. We previously showed that the human brain is surveyed by a specific pool of CD8+, and to a lesser extent CD4+, T cells with an effector-type phenotype, limited expression of cytolytic enzymes, and high expression of the IL-7 receptor (CD127), indicating maintenance by homeostatic proliferation (Smolders et al, Acta Neuropathol 2013; 126:525-35). Whether these cells represent TRM cells has remained unknown.
We currently characterize the phenotypical and functional characteristics of human brain CD8+ T cells, by assessing differentiation status, transcription factor profiles, chemokine receptor profiles, and expression of cytokines and lytic enzymes by flow cytometry. Our data indicate that brain CD8+ T cells are represented by two subsets of CD69+CD103− and CD69+CD103+ T cells. CD103 expression in brain CD8+ TRM cells correlates with enhanced differentiation, parenchymal localization, and restricted cytotoxic capacity, marking them as TRM cells.