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* Department of Pathology and
Vision Immunology Center, University of Connecticut Health Center, Farmington
Correspondence: Robert E. Cone, Ph.D., Department of Pathology, School of Medicine, The University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030-3105. E-mail: Cone{at}idx.uchc.edu
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 
,ß 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.
Key Words: NK T cells • thymus • immunoregulation • immune deviation
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