title: Loss of the surface antigen 3G11 characterizes a distinct population of anergic/regulatory T cells in experimental autoimmune encephalomyelitis.
abstract: T cell anergy is an important mechanism in the induction of peripheral tolerance against autoimmune diseases, yet no surface marker unique to anergic T cells in these diseases has been identified. In this study we induced in vivo anergy by i.v. tolerance against experimental autoimmune encephalomyelitis in myelin basic protein TCR transgenic mice, and showed that the hyporesponsiveness of autoantigen-reactive T cells from tolerized mice was associated with a dramatic loss of 3G11, a cell surface molecule on the surface of CD4+ T cells. Purified 3G11-CD4+ T cells lost autoantigen-induced proliferation and IL-2 production, whereas 3G11+CD4+ T cells retained responsiveness. Furthermore, 3G11- T cells actively suppressed proliferation and Th1 cytokine production of 3G11+ T cells and splenocytes of nontolerized mice. Active suppression by 3G11- T cells was at least partially due to soluble immunoregulatory factors, including IL-10. The T regulatory property of 3G11- T cells was confirmed in vivo because the transfer of purified 3G11- T cells effectively suppressed clinical experimental autoimmune encephalomyelitis. We conclude that loss of the surface molecule 3G11 characterizes a distinct population of anergic/regulatory T cells. This is the first demonstration of the ability to identify and purify anergic T cells by a distinct cell surface marker in an autoimmune disease and paves the way for a better understanding of the mechanism of tolerance in autoimmune diseases.
authors.affiliation: Department of Neurology, Thomas Jefferson University, 900 Walnut Street, Philadelphia, PA 19107, USA.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Shuo
authors.initials: S
authors.lastname: Yu
authors.forename: Divina
authors.initials: D
authors.lastname: Calida
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Bruno
authors.initials: B
authors.lastname: Gran
authors.forename: Malek
authors.initials: M
authors.lastname: Kamoun
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000954:Antigens, Surface; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C509654:antigen 3G11, mouse; D019041:L-Selectin; D016753:Interleukin-10; D015847:Interleukin-4