TY - JOUR
T1 - Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants
AU - Ortega, Sterling B.
AU - Kashi, Venkatesh P.
AU - Cunnusamy, Khrishen
AU - Franco, Jorge
AU - Karandikar, Nitin J.
N1 - Funding Information:
The authors thank Thomas Lee and Wallace Baldwin for technical assistance; and Ibrahim Noorbhai, Katie Poinsatte, and Drs. Ethan Baughman, Todd Eagar, Mihail Firan, Sushmita Sinha, and Ann M. Stowe for discussions and critical reading of this manuscript. These studies were supported, in part, by grants (to N.J.K.) from the NIH and the National Multiple Sclerosis Society.
Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2015
Y1 - 2015
N2 - Objective: To determine the antigenic determinants and specific molecular requirements for the generation of autoregulatory neuroantigen-specific CD81 T cells in models of multiple sclerosis (MS). Methods: We have previously shown that MOG35-55-specific CD81 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 CD81 T cells. Results: We demonstrate that alternative myelin peptides (PLP178-191) and other susceptible mouse strains (SJL) generated myelin-specific CD81 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 CD81 T cells was not affected by thymic selection, but was dependent on the presence of both CD41 and CD81 T-cell epitopes in the immunizing encephalitogenic antigen. Conclusions: These studies show that the generation of autoregulatory CD81 T cells is a more generalized, antigen-specific phenomenon across multiple neuroantigens and mouse strains, with significant implications in understanding disease regulation.
AB - Objective: To determine the antigenic determinants and specific molecular requirements for the generation of autoregulatory neuroantigen-specific CD81 T cells in models of multiple sclerosis (MS). Methods: We have previously shown that MOG35-55-specific CD81 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 CD81 T cells. Results: We demonstrate that alternative myelin peptides (PLP178-191) and other susceptible mouse strains (SJL) generated myelin-specific CD81 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 CD81 T cells was not affected by thymic selection, but was dependent on the presence of both CD41 and CD81 T-cell epitopes in the immunizing encephalitogenic antigen. Conclusions: These studies show that the generation of autoregulatory CD81 T cells is a more generalized, antigen-specific phenomenon across multiple neuroantigens and mouse strains, with significant implications in understanding disease regulation.
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U2 - 10.1212/NXI.0000000000000170
DO - 10.1212/NXI.0000000000000170
M3 - Article
C2 - 26587555
AN - SCOPUS:84952918668
SN - 2332-7812
VL - 2
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 6
M1 - e170
ER -