CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site.
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 self-tolerance and their defects in autoimmunity.
Sonoda
K H
KH
Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Exley
M
M
Snapper
S
S
Balk
S P
SP
Stein-Streilein
J
J
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D002478:Cells, Cultured; D005123:Eye / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*
D018949:Antigens, CD1; D010047:Ovalbumin