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Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber‐associated immune deviation
Author(s) -
Wang Yafei,
Goldschneider Irving,
O’Rourke James,
Cone Robert E.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.5.741
Subject(s) - biology , immunology , adoptive cell transfer , antigen , immune system , peripheral blood mononuclear cell , cd8 , spleen , t cell , t lymphocyte , biochemistry , in vitro
Injection of antigen into the anterior chamber (AC) of the eye, animmunologically privileged site, is associated with the inductionof immune deviation, as evidenced by T helper cell (Th) 1 to Th2 cellpolarization. We recently demonstrated that AC‐associated immunedeviation (ACAID) is a thymus‐dependent phenomenon initiated by the formation of regulatory α,β T‐cell receptor‐positiveCD4 − CD8 − thymocytes(THY reg s). In this study, the afferent and efferent limbsof this immunoregulatory loop were traced from peripheral blood to thethymus and then to the spleen by adoptive‐transfer assays. The resultsdemonstrate that (1) F4/80 + CD1 + peripheralblood mononuclear cells from mice whose ACs were injected withtrinitrophenol‐bovine serum albumin induce the appearance ofnatural killer (NK) 1.1 + THY reg innaïve recipients within 24 h of intravenous infusion; (2)these NK THY reg s induce (or generate) suppressor‐effector Tcells in the spleens of adoptive recipients; (3) thesesuppressor‐effector spleen cells, but not the NK THY reg sthemselves, directly inhibit the expression of delayed‐typehypersensitivity in sensitized recipients; and (4) peripheral bloodmononuclear cells from AC‐injected mice do not induce ACAID inthymectomized recipients. These results confirm our hypothesis thatACAID is a model of centrally induced dominant tolerance mediated byCD‐1‐dependent NK T cells of recent thymic origin. The results alsoprovide evidence of a novel tolerance induction pathway by whichblood‐borne antigen‐presenting cells generated by antigen injectioninto an immunologically privileged site transport antigen to the thymusand induce the formation and export of THY reg .