title: Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen.
abstract: To date, very few Ag-based regimens have been defined that could expand T regulatory (Treg) cells to reverse autoimmunity. Additional understanding of Treg function with respect to specificity and broad suppression should help overcome these limitations. Ig-proteolipid protein (PLP)1, an Ig carrying a PLP1 peptide corresponding to amino acid residues 139-151 of PLP, displayed potent tolerogenic functions and proved effective against experimental allergic encephalomyelitis (EAE). In this study, we took advantage of the Ig-PLP1 system and the PLP1-specific TCR transgenic 5B6 mouse to define a regimen that could expand Ag-specific Treg cells in vivo and tested for effectiveness against autoimmunity involving diverse T cell specificities. The findings indicate that in vivo exposure to aggregated Ig-PLP1 drives PLP1-specific 5B6 TCR transgenic cells to evolve as Treg cells expressing CD25, CTLA-4, and Foxp3 and producing IL-10. These Treg cells were able to suppress PLP1 peptide-induced EAE in both SJL/J and F(1) (SJL/J x C57BL/6) mice. However, despite being effective against disease induced with a CNS homogenate, the Treg cells were unable to counter EAE induced by a myelin basic protein or a myelin oligodendrocyte glycoprotein peptide. Nevertheless, activation with Ag before transfer into the host mice supports suppression of both myelin oligodendrocyte glycoprotein- and myelin basic protein peptide-induced EAE. Thus, it is suggested that activation of Treg cells by the cognate autoantigen is necessary for operation of broad suppressive functions.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, 65212, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Randal K
authors.initials: RK
authors.lastname: Gregg
authors.forename: J Jeremiah
authors.initials: JJ
authors.lastname: Bell
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Rohit
authors.initials: R
authors.lastname: Divekar
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Renu
authors.initials: R
authors.lastname: Jain
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Waldner
authors.forename: John C
authors.initials: JC
authors.lastname: Hardaway
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D024201:Bystander Effect / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012008:Recurrence; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
chemical_list: D018984:Epitopes, T-Lymphocyte; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C435023:myelin proteolipid protein (139-151)