Educational Note

Antigen-specific autoreactive T cell responses targeting the central nervous system

Running title: Autoreactive T cells and central nervous system

Efthimios Dardiotis1*, 1 Dimitrios P. Bogdanos2

1Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University General Hospital of Larissa, 41110 Larissa, Greece

2Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University General Hospital of Larissa, 41110 Larissa, Greece

*Corresponding Author’s e-mail: edar@med.uth.gr

(submitted 25 May 2022; revised 5 June 2022; accepted 7 June 2022)

Keywords– Autoimmuniity; Adverse reactions; autoimmunity; autoimmune rheumatic diseases; cyclosporine; gum hypertrophy; treatment

Fig. 1 Activation of antigen-specific autoreactive CD4+ T lymphocytes showing the possible paths of activated T cell entry Based on a consise review by (1). CD4+ T cells are most likely primed in the periphery by professional antigen presenting cells (APC) i.e. dendritic cells (DCs), which present autoantigenic epitopes such as myelin or other disease-related epitopes (2). In turn, APCs residing in the central nervous system (CNS) can seize these autoantigens in situ and migrate them to the lymph nodes. Antigen-specific autoreactive CD4+ T cells cross the blood–cerebrospinal fluid (CSF) barrier and enter the subarachnoid space.

Those T cells are re-activated within the subarachnoid space by HLA class II-expressing macrophages and DCs expressing various autoepitopes enter the subarachnoid space in the choroid plexus. Reactivated T cells and their immune counterparts release soluble mediators and trigger a series of events damaging the myelin sheath, ultimately leading to demyelination (1-5) (prepared using a template by BioRender under a license to DPB).

References

1. Goverman J. Autoimmune T cell responses in the central nervous system. Nat Rev Immunol. 2009;9(6):393-407.

2. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA, Jr. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med. 1993;177(1):57-68.

3. Florou DT, Mavropoulos A, Dardiotis E, Tsimourtou V, Siokas V, Aloizou AM, et al. Tetracyclines Diminish In Vitro IFN-gamma and IL-17-Producing Adaptive and Innate Immune Cells in Multiple Sclerosis. Front Immunol. 2021;12:739186.

4. Kivisakk P, Imitola J, Rasmussen S, Elyaman W, Zhu B, Ransohoff RM, et al. Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis. Ann Neurol. 2009;65(4):457-69.

5. Vasileiadis GK, Dardiotis E, Mavropoulos A, Tsouris Z, Tsimourtou V, Bogdanos DP, et al. Regulatory B and T lymphocytes in multiple sclerosis: friends or foes? Auto Immun Highlights. 2018;9(1):9.

AUTHORS CONTRIBUTION

The authors prepared the manuscript and the artwork. The authors approvesdthe final version of the manuscript.

CONFLICT OF INTEREST

The Authors declare no conflict of interest