title: Autoregulatory CD8 T cells depend on cognate antigen recognition and CD4/CD8 myelin determinants.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sterling B
authors.initials: SB
authors.lastname: Ortega
authors.affiliation: 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.
authors.forename: Venkatesh P
authors.initials: VP
authors.lastname: Kashi
authors.affiliation: 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.
authors.forename: Khrishen
authors.initials: K
authors.lastname: Cunnusamy
authors.affiliation: 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.
authors.forename: Jorge
authors.initials: J
authors.lastname: Franco
authors.affiliation: 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.
authors.forename: Nitin J
authors.initials: NJ
authors.lastname: Karandikar