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Characteristics of differentiated CD8(+) and CD4 (+) T cells present in the human brain.
- Source :
-
Acta neuropathologica [Acta Neuropathol] 2013 Oct; Vol. 126 (4), pp. 525-35. Date of Electronic Publication: 2013 Jul 24. - Publication Year :
- 2013
-
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.
- Subjects :
- Aged
Aged, 80 and over
Alzheimer Disease pathology
Autopsy
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes enzymology
CD8-Positive T-Lymphocytes enzymology
Corpus Callosum cytology
Female
Flow Cytometry
Humans
Immunohistochemistry
Interleukin-7 metabolism
Interleukin-7 Receptor alpha Subunit metabolism
Lymphocyte Count
Male
Middle Aged
Netherlands
Phenotype
Receptors, CXCR3 metabolism
Receptors, Interleukin-8A metabolism
Tissue Banks
Brain cytology
CD4-Positive T-Lymphocytes physiology
CD8-Positive T-Lymphocytes physiology
Cell Differentiation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0533
- Volume :
- 126
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica
- Publication Type :
- Academic Journal
- Accession number :
- 23880787
- Full Text :
- https://doi.org/10.1007/s00401-013-1155-0