CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site

被引:287
作者
Sonoda, KH
Exley, M
Snapper, S
Balk, SP
Stein-Streilein, J
机构
[1] Harvard Univ, Sch Med, Canc Biol Program,Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA
[2] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA
[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care,Dept Med, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA
关键词
innate immunity; immune deviation; anterior chamber-associated immune deviation autoimmunity; i.v; tolerance;
D O I
10.1084/jem.190.9.1215
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Systemic tolerance can be elicited by introducing antigen into an immune-privileged site, such as the eye, or directly into the blood. Both routes of immunization result in a selective deficiency of systemic delayed type hypersensitivity. Although the experimental animal model of anterior chamber-associated immune deviation (ACAID) occurs in most mouse strains, ACAID cannot be induced in several mutant mouse strains that are coincidentally deficient in natural killer T (NKT) cells. Therefore, this model for immune-privileged site-mediated tolerance provided us with an excellent format for studying the role of NKT cells in the development of tolerance. The following data show that CD1-reactive NKT cells are required for the development of systemic tolerance induced via the eye as follows: (a) CD1 knockout mice were unable to develop ACAID unless they were reconstituted with NKT cells together with CD1(+) antigen-presenting cells; (b) specific antibody depletion of NKT cells in vivo abrogated the development of ACAID; and (c) anti-CD1 monoclonal antibody treatment of wild-type mice prevented ACAID development. Significantly, CD1-reactive NKT cells were not required for intravenously induced systemic tolerance, thereby establishing that different mechanisms mediate development of tolerance to antigens inoculated by these routes. A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in sell-tolerance and their defects in autoimmunity.
引用
收藏
页码:1215 / 1225
页数:11
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