title: Characteristics of differentiated CD8(+) and CD4 (+) T cells present in the human brain.
abstract: Immune surveillance of the central nervous system (CNS) by T cells is important to keep CNS-trophic viruses in a latent state, yet our knowledge of the characteristics of CNS-populating T cells is incomplete. We performed a comprehensive, multi-color flow-cytometric analysis of isolated T cells from paired corpus callosum (CC) and peripheral blood (PB) samples of 20 brain donors. Compared to PB, CC T cells, which were mostly located in the perivascular space and sporadically in the parenchyma, were enriched for cells expressing CD8. Both CD4(+) and CD8(+) T cells in the CC had a late-differentiated phenotype, as indicated by lack of expression of CD27 and CD28. The CC contained high numbers of T cells expressing chemokine receptor CX3CR1 and CXCR3 that allow for homing to inflamed endothelium and tissue, but hardly cells expressing the lymph node-homing receptor CCR7. Despite the late-differentiated phenotype, CC T cells had high expression of the IL-7 receptor α-chain CD127 and did not contain the neurotoxic cytolytic enzymes perforin, granzyme A, and granzyme B. We postulate that CNS T cells make up a population of tissue-adapted differentiated cells, which use CX3CR1 and CXCR3 to home into the perivascular space, use IL-7 for maintenance, and lack immediate cytolytic activity, thereby preventing immunopathology in response to low or non-specific stimuli. The presence of these cells in this tightly regulated environment likely enables a fast response to local threats. Our results will enable future detailed exploration of T-cell subsets in the brain involved in neurological diseases.
authors.affiliation: Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Smolders
authors.forename: Ester B M
authors.initials: EB
authors.lastname: Remmerswaal
authors.forename: Karianne G
authors.initials: KG
authors.lastname: Schuurman
authors.forename: Jeroen
authors.initials: J
authors.lastname: Melief
authors.forename: Corbert G
authors.initials: CG
authors.lastname: van Eden
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Inge
authors.initials: I
authors.lastname: Huitinga
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000166:cytology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D003337:Corpus Callosum / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D015851:Interleukin-7 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D054367:Receptors, CXCR3 / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D014015:Tissue Banks
chemical_list: D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D054367:Receptors, CXCR3; D023062:Receptors, Interleukin-8A