MIP-2 recruits NKT cells to the spleen during tolerance induction.
Peripheral tolerance occurs after intraocular administration of Ag and is dependent on an increase in splenic NKT cells. New data here show that macrophage inflammatory protein-2 (MIP-2) is selectively up-regulated in tolerance-conferring APCs and serves to recruit NKT cells to the splenic marginal zone, where they form clusters with APCs and T cells. In the absence of the high-affinity receptor for MIP-2 (as in CXCR2-deficient mice) or in the presence of a blocking Ab to MIP-2, peripheral tolerance is prevented, and Ag-specific T regulatory cells are not generated. Understanding the regulation of lymphocyte traffic during tolerance induction may lead to novel therapies for autoimmunity, graft acceptance, and tumor rejection.
Faunce
D E
DE
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Sonoda
K H
KH
Stein-Streilein
J
J
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage; D000943:Antigens, Differentiation / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000941:Antigens; D000943:Antigens, Differentiation; D017252:CD3 Complex; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; C036763:monocyte-macrophage differentiation antigen; D010047:Ovalbumin