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L. Luus, J. Zhang–Hoover, J. Stein–Streilein; ACAID Mechanisms Common to Low Dose Oral Tolerance Are Not Involved in S.C. Induced Tolerance . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5156.
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Peripheral immune tolerance established by introducing antigen into the anterior chamber of the eye (ACAID) and low dose oral tolerance both require invariant (i)NKT cells for the generation of efferent CD8+ T regulatory cells. Although iNKT cells are not involved in the induction of i.v. tolerance, the extent to which these cells are required in other models of tolerance is not well studied. Since tolerance may be induced by inoculation of antigen without adjuvant via the subcutaneous (s.c.) route, we postulated that iNKT cells might play a role in s.c. induced tolerance.
OVA in PBS was injected s.c. into mice in the footpad; tolerance was assessed by the suppression of IFN–γ production in vitro, or reduced delayed hypersensitivity (DH) responses following deliberate immunization of the mice with s.c. OVA in CFA followed by ear pinnae challenge with antigen. The role of iNKT cells was tested by s.c. inoculation of OVA prior to sensitization in Jα18 KO mice lacking iNKT cells. The generation of regulatory cells was tested by transferring spleen cells or lymph node cells from the s.c. inoculated mice to naïve mice prior to testing for a DH response.
Subcutaneous inoculation of OVA suppressed IFN–γ production in vitro, and resulted in suppression of DH responses in both WT and Jα18 KO mice. However, unlike ACAID, the s.c. induced suppression was not transferable with spleen cells or lymph node cells.
Antigen tolerance induced via the anterior chamber and via the s.c route differ in their mechanisms of expression. As in ACAID, antigen given s.c. in the absence of CFA induces suppression of DH in vivo, and of IFN–γ production in vitro. In contrast to ACAID, s.c. tolerance could not be adoptively transferred to naïve mice. We postulate that the subcutaneous antigen presenting cells that process and present antigen lack the ability of F4/80+ antigen presenting cells in the eye to induce efferent T regulatory cells. This work was supported by NIH grant EY 11983.
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