Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants

Sterling B Ortega; Venkatesh P Kashi; Khrishen Cunnusamy; Jorge Franco; Nitin J Karandikar

doi:10.1212/NXI.0000000000000170

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Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants

Journal article

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Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants

Sterling B Ortega, Venkatesh P Kashi, Khrishen Cunnusamy, Jorge Franco and Nitin J Karandikar

Neurology : neuroimmunology & neuroinflammation, Vol.2(6), pp.e170-e170

12/2015

DOI: 10.1212/NXI.0000000000000170

PMCID: PMC4635551

PMID: 26587555

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Abstract

To determine the antigenic determinants and specific molecular requirements for the generation of autoregulatory neuroantigen-specific CD8(+) T cells in models of multiple sclerosis (MS). We have previously shown that MOG35-55-specific CD8(+) T cells suppress experimental autoimmune encephalomyelitis (EAE) in the C57BL/6 model. In this study, we utilized multiple models of EAE to assess the ability to generate autoregulatory CD8(+) T cells. We demonstrate that alternative myelin peptides (PLP178-191) and other susceptible mouse strains (SJL) generated myelin-specific CD8(+) T cells, which were fully capable of suppressing disease. The disease-ameliorating function of these cells was dependent on the specific cognate myelin antigen. Generation of these autoregulatory CD8(+) T cells was not affected by thymic selection, but was dependent on the presence of both CD4(+) and CD8(+) T-cell epitopes in the immunizing encephalitogenic antigen. These studies show that the generation of autoregulatory CD8(+) T cells is a more generalized, antigen-specific phenomenon across multiple neuroantigens and mouse strains, with significant implications in understanding disease regulation.

Details

Title: Subtitle: Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants
Creators: Sterling B Ortega - Departments of Pathology (S.B.O., V.P.K., K.C., J.F., N.J.K.) and Neurology and Neurotherapeutics (S.B.O., N.J.K.), UT Southwestern Medical Center, Dallas, TX; and the Department of Pathology (N.J.K.), University of Iowa, Iowa City
Venkatesh P Kashi - Departments of Pathology (S.B.O., V.P.K., K.C., J.F., N.J.K.) and Neurology and Neurotherapeutics (S.B.O., N.J.K.), UT Southwestern Medical Center, Dallas, TX; and the Department of Pathology (N.J.K.), University of Iowa, Iowa City
Khrishen Cunnusamy - Departments of Pathology (S.B.O., V.P.K., K.C., J.F., N.J.K.) and Neurology and Neurotherapeutics (S.B.O., N.J.K.), UT Southwestern Medical Center, Dallas, TX; and the Department of Pathology (N.J.K.), University of Iowa, Iowa City
Jorge Franco - Departments of Pathology (S.B.O., V.P.K., K.C., J.F., N.J.K.) and Neurology and Neurotherapeutics (S.B.O., N.J.K.), UT Southwestern Medical Center, Dallas, TX; and the Department of Pathology (N.J.K.), University of Iowa, Iowa City
Nitin J Karandikar - Departments of Pathology (S.B.O., V.P.K., K.C., J.F., N.J.K.) and Neurology and Neurotherapeutics (S.B.O., N.J.K.), UT Southwestern Medical Center, Dallas, TX; and the Department of Pathology (N.J.K.), University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: Neurology : neuroimmunology & neuroinflammation, Vol.2(6), pp.e170-e170
DOI: 10.1212/NXI.0000000000000170
PMID: 26587555
PMCID: PMC4635551
NLM abbreviation: Neurol Neuroimmunol Neuroinflamm
ISSN: 2332-7812
eISSN: 2332-7812
Publisher: United States
Grant note: R01 AI065463 / NIAID NIH HHS K24 AI079272 / NIAID NIH HHS
Language: English
Date published: 12/2015
Academic Unit: Pathology
Record Identifier: 9984047634902771

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