Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber-associated immune deviation.
Injection of antigen into the anterior chamber (AC) of the eye, an immunologically privileged site, is associated with the induction of immune deviation, as evidenced by T helper cell (Th) 1 to Th2 cell polarization. We recently demonstrated that AC-associated immune deviation (ACAID) is a thymus-dependent phenomenon initiated by the formation of regulatory alpha,beta T-cell receptor-positive CD4(-) CD8(-) thymocytes (THYregs). In this study, the afferent and efferent limbs of this immunoregulatory loop were traced from peripheral blood to the thymus and then to the spleen by adoptive-transfer assays. The results demonstrate that (1) F4/80(+) CD1(+) peripheral blood mononuclear cells from mice whose ACs were injected with trinitrophenol-bovine serum albumin induce the appearance of natural killer (NK) 1.1(+) THYreg in naïve recipients within 24 h of intravenous infusion; (2) these NK THYregs induce (or generate) suppressor-effector T cells in the spleens of adoptive recipients; (3) these suppressor-effector spleen cells, but not the NK THYregs themselves, directly inhibit the expression of delayed-type hypersensitivity in sensitized recipients; and (4) peripheral blood mononuclear cells from AC-injected mice do not induce ACAID in thymectomized recipients. These results confirm our hypothesis that ACAID is a model of centrally induced dominant tolerance mediated by CD-1-dependent NK T cells of recent thymic origin. The results also provide evidence of a novel tolerance induction pathway by which blood-borne antigen-presenting cells generated by antigen injection into an immunologically privileged site transport antigen to the thymus and induce the formation and export of THYreg.
Wang
Y
Y
Department of Pathology and Vision Immunology Center, University of Connecticut Health Center, Farmington, USA.
Goldschneider
I
I
O'Rourke
J
J
Cone
R E
RE
D019264:Adoptive Transfer; D000818:Animals; D000869:Anterior Eye Segment / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; D018949:Antigens, CD1; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins