Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis

Nathan R. York, Jason P. Mendoza, Sterling B. Ortega, Andrew Benagh, Andrew F. Tyler, Mihail Firan, Nitin J. Karandikar

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Immune-based self-recognition and failure to modulate this response are believed to contribute to the debilitating autoimmune pathology observed in multiple sclerosis (MS). Studies from its murine model, experimental autoimmune encephalomyelitis (EAE), have shown that neuroantigen-specific CD4+T cells are capable of inducing disease, while their immune sibling, the CD8+T cells, have largely been ignored. To understand their role in autoimmune demyelination, we first confirmed that, similar to our observations in human MS, there is robust induction of neuroantigen-reactive CD8+T cells in several models, including MOG35-55/CFA-induced EAE. However, MOG35-55-specific CD8+T-cells, when purified, were unable to adoptively transfer disease into naïve mice (in contrast to CD4+T-cells). In fact, we observed that the transfer of these neuroantigen-specific CD8+T cells was able to suppress the induction of EAE and to inhibit ongoing EAE. These regulatory CD8+T cells produced IFN-γ and perforin and were able to kill MOG loaded CD4+T-cells as well as CD4-depleted APC, suggesting a cytotoxic/suppressor mechanism. Inhibition of EAE was associated with both the modulation of APC function as well as decreased MOG-specific CD4+T cell responses. Our studies reveal a novel and unexpected immune regulatory function for neuroantigen-specific CD8+T cells and have interesting biologic and therapeutic implications.

Original languageEnglish (US)
Pages (from-to)33-44
Number of pages12
JournalJournal of Autoimmunity
Volume35
Issue number1
DOIs
StatePublished - Aug 2010

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Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Multiple Sclerosis
Perforin
Demyelinating Diseases
Regulatory T-Lymphocytes
Pathology

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

York, N. R., Mendoza, J. P., Ortega, S. B., Benagh, A., Tyler, A. F., Firan, M., & Karandikar, N. J. (2010). Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis. Journal of Autoimmunity, 35(1), 33-44. https://doi.org/10.1016/j.jaut.2010.01.003

Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis. / York, Nathan R.; Mendoza, Jason P.; Ortega, Sterling B.; Benagh, Andrew; Tyler, Andrew F.; Firan, Mihail; Karandikar, Nitin J.

In: Journal of Autoimmunity, Vol. 35, No. 1, 08.2010, p. 33-44.

Research output: Contribution to journalArticle

York, NR, Mendoza, JP, Ortega, SB, Benagh, A, Tyler, AF, Firan, M & Karandikar, NJ 2010, 'Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis', Journal of Autoimmunity, vol. 35, no. 1, pp. 33-44. https://doi.org/10.1016/j.jaut.2010.01.003
York, Nathan R. ; Mendoza, Jason P. ; Ortega, Sterling B. ; Benagh, Andrew ; Tyler, Andrew F. ; Firan, Mihail ; Karandikar, Nitin J. / Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis. In: Journal of Autoimmunity. 2010 ; Vol. 35, No. 1. pp. 33-44.
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