Autoantigen specific IL-2 activated CD4+CD25+T regulatory cells inhibit induction of experimental autoimmune neuritis

Giang T Tran; Suzanne J Hodgkinson; Nicole Carter; Nirupama D Verma; Catherine M Robinson; Karren M Plain; Masaru Nomura; Bruce M Hall

doi:10.1016/j.jneuroim.2020.577186

Autoantigen specific IL-2 activated CD4⁺CD25⁺T regulatory cells inhibit induction of experimental autoimmune neuritis

J Neuroimmunol. 2020 Apr 15:341:577186. doi: 10.1016/j.jneuroim.2020.577186. Epub 2020 Feb 3.

Authors

Giang T Tran¹, Suzanne J Hodgkinson², Nicole Carter³, Nirupama D Verma⁴, Catherine M Robinson⁵, Karren M Plain⁶, Masaru Nomura⁷, Bruce M Hall⁸

Affiliations

¹ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia. Electronic address: [email protected].
² Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia; Departments of Neurology Liverpool Health Service, Liverpool, NSW, Australia. Electronic address: [email protected].
³ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia. Electronic address: [email protected].
⁴ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia. Electronic address: [email protected].
⁵ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia. Electronic address: [email protected].
⁶ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia. Electronic address: [email protected].
⁷ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia.
⁸ Immune Tolerance Laboratory, Faculty of Medicine, UNSW Sydney, Ingham Institute, Liverpool, NSW, Australia; Department of Nephrology, Liverpool Health Service, Liverpool, NSW, Australia. Electronic address: [email protected].

PMID: 32058174
DOI: 10.1016/j.jneuroim.2020.577186

Abstract

Experimental autoimmune neuritis (EAN) induced by peripheral nerve myelin (PNM) is self-limiting and re-immunization with PNM does not re-activate disease. This study showed inhibition of EAN by CD4⁺CD25⁺T cells both from sensitized hosts or from naïve hosts after ex-vivo activation by PNM and rIL-2. Transfer of naïve CD4⁺CD25⁺T cells has no effect on EAN, nor did naïve CD4⁺CD25⁺T cells activated with rIL-2 and renal tubular antigen. Culture of naive CD4⁺CD25⁺Treg with rIL-2 and PNM induced mRNA for the IFN-gamma receptor. We showed naïve CD4⁺CD25⁺T cells activated by specific auto-antigen and rIL-2 produced more potent antigen-specific Treg that may have therapeutic potential.

Keywords: Autoimmunity; Experimental autoimmune neuritis; Interleukin-2; T regulatory cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoantigens / immunology*
CD4 Antigens / analysis
Cells, Cultured
Convalescence
Female
Immunotherapy, Adoptive*
Interleukin-2 / pharmacology*
Interleukin-2 Receptor alpha Subunit / analysis
Lymphocyte Activation / drug effects
Myelin Sheath / immunology
Neuritis, Autoimmune, Experimental / immunology*
Neuritis, Autoimmune, Experimental / prevention & control
Rats
Rats, Inbred Lew
Recombinant Proteins / pharmacology
Recurrence
T-Cell Antigen Receptor Specificity
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / transplantation

Substances

Autoantigens
CD4 Antigens
Interleukin-2
Interleukin-2 Receptor alpha Subunit
Recombinant Proteins