T cell recognition of rat myelin basic protein as a TCR antagonist inhibits reciprocal activation of antigen-presenting cells and engenders resistance to experimental autoimmune encephalomyelitis.
The aim of this study was to assess whether T cell recognition of myelin basic protein (MBP) as a partially antagonistic self antigen regulates the reciprocal activation of professional antigen-presenting cells (APC). This study focused on the rat 3H3 T cell clone that recognized guinea pig (GP) MBP as a full agonist and self rat (R) MBP as a partial agonist. In cultures of 3H3 T cells and splenic APC, the agonist GPMBP elicited several responses by splenic APC, including production of nitric oxide, down-regulation of I-A, induction of B7.1 and B7.2, and prolongation of APC survival. RMBP stimulated a partial increase in production of nitric oxide, partially promoted survival of splenic APC, but did not alter expression of I-A, B7.1, or B7.2 on splenic APC. In the presence ofGPMBP, RMBP antagonized agonist-stimulated induction of B7 molecules, reversed the loss of I-A, and promoted the generation of I-A(+), costimulus-deficient APC. Furthermore, 3H3 T cells cultured with RMBP and irradiated splenocytes reduced the severity of EAE upon adoptive transfer into naive rat recipients subsequently challenged with an encephalitogenic dose of GPMBP/CFA. Overall, this study indicates that T cell receptor antagonism blocks T cell activation, inhibits feedback activation of splenic APC, and promotes T cell-dependent regulatory activities in EAE.
Walker
M R
MR
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.
Mannie
M D
MD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002470:Cell Survival; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007113:Immunity, Innate / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D004676:Myelin Basic Protein / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D001324:Autoantigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D009569:Nitric Oxide