CD1d on antigen‐transporting APC and splenic marginal zone B cells promotes NKT cell‐dependent tolerance

• Published in: European journal of immunology Vol. 32; no. 3; pp. 848 - 857
• Main Authors: Sonoda, Koh‐Hei, Stein‐Streilein, Joan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.03.2002
• Subjects: Adoptive Transfer; Animals; Antigen-Presenting Cells - immunology; Antigens, CD1 - genetics; Antigens, CD1 - immunology; Antigens, CD1d; Ascitic Fluid - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - transplantation; CD1d; CD1d antigen; Cells, Cultured - immunology; Chimera; Crosses, Genetic; Eye - immunology; Female; Hypersensitivity, Delayed - immunology; Immune Tolerance - immunology; Innate immunity; Killer Cells, Natural - immunology; Lymphocyte Activation; MHC class I‐like molecule; Mice; Mice, Inbred C57BL; Mice, Knockout; NKT cell; Peripheral tolerance; Spleen - cytology; Transforming Growth Factor beta - pharmacology; transforming growth factor-^b2
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200203)32:3<848::AID-IMMU848>3.0.CO;2-I

CD1d‐reactive NKT cells are required for the development of antigen‐specific T regulatory (Tr) cells responsible for mediating systemic tolerance induced through an immune privileged site suchas the eye. The aim of this study was to elucidate the cellular source of CD1d needed for NKT cell activation. Transforming growth factor β (TGFβ)‐2‐treated peritoneal exudate cells (PEC) functionally resemble "eye‐derived" antigen‐presenting cells (APC) and contribute to the generation of Tr cells both in vitro and in vivo. However, when TGFβ‐2‐treated PEC were pretreated with CD1d‐specific antibodies or lacked CD1d expression they failed to induce Tr cells. In addition, we show that the subpopulation of marginal zone (MZ) B cells within the spleen is necessary for induction of Tr cells and that they also must express CD1d. The role of MZ B in tolerance is novel and previously unexplored. Thus, CD1d is necessarily expressed on putative eye‐derived APC and splenic MZ B cells for efficient generation of Tr cells in CD1d‐reactive NKT cell‐dependent tolerance.