title: Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves' disease may carry functional consequences for disease pathogenesis.
abstract: Graves' disease (GD), an autoimmune process involving thyroid and orbital tissue, is associated with lymphocyte abnormalities including expansion of memory T cells. Insulin-like growth factor receptor-1 (IGF-1R)-bearing fibroblasts overpopulate connective tissues in GD. IGF-1R on fibroblasts, when ligated with IgGs from these patients, results in the expression of the T cell chemoattractants, IL-16 and RANTES. We now report that a disproportionately large fraction of peripheral blood T cells express IGF-1R (CD3+IGF-R+). CD3+IGF-1R+ T cells comprise 48 +/- 4% (mean +/- SE; n = 33) in patients with GD compared with 15 +/- 3% (n = 21; p < 10(-8)) in controls. This increased population of IGF-1R+ T cells results, at least in part, from an expansion of CD45RO+ T cells expressing the receptor. In contrast, the fraction of CD45RA+IGF-1R+ T cells is similar in GD and controls. T cells harvested from affected orbital tissues in GD reflect similar differences in the proportion of IGF-1R+CD3+ and IGF-1R+CD4+CD3+ cells as those found in the peripheral circulation. GD-derived peripheral T cells express durable, constitutive IGF-1R expression in culture and receptor levels are further up-regulated following CD3 complex activation. IGF-1 enhanced GD-derived T cell incorporation of BrdU (p < 0.02) and inhibited Fas-mediated apoptosis (p < 0.02). These findings suggest a potential role for IGF-1R displayed by lymphocytes in supporting the expansion of memory T cells in GD.
authors.affiliation: Department of Medicine, Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA.
authors.forename: Raymond S
authors.initials: RS
authors.lastname: Douglas
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Gianoukakis
authors.forename: Shweta
authors.initials: S
authors.lastname: Kamat
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006111:Graves Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007156:Immunologic Memory; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018946:Chemokine CCL5; D019410:Interleukin-16; D019014:fas Receptor; D017526:Receptor, IGF Type 1