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  • Review Article
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T cell responses in the central nervous system

Nature Reviews Immunology volume 17, pages 179–194 (2017)Cite this article

Subjects

Key Points

  • The meningeal linings of the central nervous system (CNS) undergo intense immunosurveillance and have efficient lymphatic drainage. This allows adaptive immune responses to be primed in the deep cervical lymph nodes against antigens derived from the meningeal compartment.

  • T cell responses against CNS-expressed self-antigens may develop as a result of T cells being primed by mimotopes of these self-antigens in the lymph nodes that drain peripheral tissues and the subsequent aberrant homing of such antigen-specific T cells into the CNS compartment.

  • Reactivation of antigen-experienced T cells within the CNS occurs in distinct anatomical compartments: namely, in the perivascular space of parenchymal post-capillary venules, in the meninges and in the choroid plexus. Each site represents a distinct functional compartment owing to the presence of unique types of antigen-presenting cells.

  • Different T helper (TH) cell subsets use distinct homing molecules to gain access to the CNS parenchyma, and this differential usage may determine the preferential homing of TH1 cells and TH17 cells to different parts of the CNS.

  • Within the inflamed CNS, TH cells exhibit a high degree of plasticity, and the molecular basis of this is becoming increasingly understood. For example, the expression of the transcriptional regulator B lymphocyte-induced maturation protein 1 (BLIMP1) is essential for the conversion of pathogenic TH cells into IL-10 producing regulatory T cells.

  • Forkhead box P3 (FOXP3)-expressing regulatory T cells are dispensable for maintaining immune tolerance in the CNS in the steady state, but these cells are indispensable for re-establishing homeostasis in the inflamed CNS.

  • After viral infection of the CNS, self-renewing populations of tissue-resident memory CD8+ T cells (TRM cells) are generated. These TRM cells exhibit a distinct transcriptional and phenotypic profile, and represent an autonomous line of defence that protects against re-infection or recrudescence of latent viral infections in the CNS.

Abstract

T cells are required for immune surveillance of the central nervous system (CNS); however, they can also induce severe immunopathology in the context of both viral infections and autoimmunity. The mechanisms that are involved in the priming and recruitment of T cells to the CNS are only partially understood, but there has been renewed interest in this topic since the 'rediscovery' of lymphatic drainage from the CNS. Moreover, tissue-resident memory T cells have been detected in the CNS and are increasingly recognized as an autonomous line of host defence. In this Review, we highlight the main mechanisms that are involved in the priming and CNS recruitment of CD4+ T cells, CD8+ T cells and regulatory T cells. We also consider the plasticity of T cell responses in the CNS, with a focus on viral infection and autoimmunity.

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Figure 1: T cell immunity in the central nervous system.
Figure 2: T cell 'ports of entry' into the central nervous system are characterized by distinct antigen-presenting cell populations.
Figure 3: T helper cell subsets and central nervous system inflammation.
Figure 4: Molecular basis of T helper 17 cell plasticity at sites of inflammation.
Figure 5: Immune surveillance in the central nervous system by different memory T cell populations.

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Acknowledgements

The authors thank A. Muschaweckh for critically reading the manuscript. Work in the authors' laboratories is supported by the Deutsche Forschungsgemeinschaft (grants TRR128, SFB1054-B07, TK and SyNergy to T.K.), by the European Research Council (EXODUS Consolidator Grant 647215 to T.K.), and the Sylvia and Charles Viertel Foundation (a Senior Medical Research Fellowship to A.K.).

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Authors and Affiliations

  1. Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, Munich, 81675, Germany

    Thomas Korn

  2. Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany

    Thomas Korn

  3. The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052, Victoria, Australia

    Axel Kallies

  4. Department of Medical Biology, University of Melbourne, Parkville, 3010, Victoria, Australia

    Axel Kallies

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  1. Thomas Korn
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Correspondence to Thomas Korn or Axel Kallies.

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Korn, T., Kallies, A. T cell responses in the central nervous system. Nat Rev Immunol 17, 179–194 (2017). https://doi.org/10.1038/nri.2016.144

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