Chemokines modulate experimental autoimmune thyroiditis through attraction of autoreactive or regulatory T cells.
A critical event in the pathogenesis of experimental autoimmune thyroiditis (EAT) is the entry of thyroid-specific T lymphocytes into the thyroid gland. To investigate the role of soluble mediators in that infiltration, we have assayed the expression of various chemokines in diseased thyroid glands and in cytokine-treated cultures of normal thyroid epithelial cells. MCP-1 (monocyte chemotactic protein-1) and RANTES are produced during EAT and induced in vitro by IFN-gamma, IL-10, TNF-alpha, and IL-1beta. In vitro chemotaxis experiments using immune lymph node (LN) cells showed that RANTES attracted mTg-specific responder LN cells, whereas MCP-1 attracted mTg-specific CD4(+), CD25(+) regulator cells that secreted IL-10. The in vivo transfer of LN T cells attracted in vitro either by RANTES or by MCP-1 confirmed their opposite effects on the course of EAT.
Goulvestre
Claire
C
Laboratoire d'Immunologie, Hôpital et Faculté de Médecine Cochin, AP-HP, Université Paris V, Paris, France.
Batteux
Frédéric
F
Charreire
Jeannine
J
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D002633:Chemotaxis; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D007375:Interleukin-1; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma