Binding of recombinant T cell receptor ligands (RTL) to antigen presenting cells prevents upregulation of CD11b and inhibits T cell activation and transfer of experimental autoimmune encephalomyelitis.
Recombinant T cell ligands (RTLs) ameliorate experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner. We evaluated effects of RTL401 (I-A(s) alpha1beta1+PLP-139-151) on splenocytes from SJL/J mice with EAE to study RTL-T cell tolerance-inducing mechanisms. RTLs bound to B, macrophages and DCs, through RTL-MHC-alpha1beta1 moiety. RTL binding reduced CD11b expression on splenic macrophages/DC, and RTL401-conditioned macrophages/DC, not B cells, inhibited T cell activation. Reduced ability of RTL- incubated splenocytes to transfer EAE was likely mediated through macrophages/DC, since B cells were unnecessary for RTL treatment of EAE. These results demonstrate a novel pathway of T cell regulation by RTL-bound APCs.
Sinha
Sushmita
S
Neuroimmunology Research R&D-31, Portland VA Medical Center, Portland, OR 97239, USA.
Miller
Lisa
L
Subramanian
Sandhya
S
McCarty
Owen J T
OJ
Proctor
Thomas
T
Meza-Romero
Roberto
R
Huan
Jianya
J
Burrows
Gregory G
GG
Vandenbark
Arthur A
AA
Offner
Halina
H
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D039481:CD11b Antigen; D008024:Ligands; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C435023:myelin proteolipid protein (139-151)