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Characteristics of differentiated CD8+ and CD4+ T cells present in the human brain

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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.

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Acknowledgments

This research was funded by the Netherlands Institute for Neuroscience. The Netherlands Brain Bank (www.brainbank.nl) is acknowledged for providing the donor material.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands

    Joost Smolders, Karianne G. Schuurman, Jeroen Melief, Corbert G. van Eden & Inge Huitinga

  2. Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Ester B. M. Remmerswaal & Jörg Hamann

  3. Division of Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands

    René A. W. van Lier

Authors
  1. Joost Smolders
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  2. Ester B. M. Remmerswaal
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  3. Karianne G. Schuurman
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  4. Jeroen Melief
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  5. Corbert G. van Eden
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  6. René A. W. van Lier
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  7. Inge Huitinga
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Correspondence to Inge Huitinga or Jörg Hamann.

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I. Huitinga and J. Hamann equally contributed to this study.

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Smolders, J., Remmerswaal, E.B.M., Schuurman, K.G. et al. Characteristics of differentiated CD8+ and CD4+ T cells present in the human brain. Acta Neuropathol 126, 525–535 (2013). https://doi.org/10.1007/s00401-013-1155-0

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