CD1d-reactive NKT Cells are Required for Induction of ACAID in Previously Sensitized Mice

Abstract

Abstract: : Purpose: Anterior chamber associated immune deviation (ACAID) induced by inoculation of antigen in the anterior chamber (a.c.) of the eye of naïve mice is dependent on CD1d reactive NKT cells. While it is known that ACAID also induces T regulatory cells in presensitized mice, it is not known if the generation of tolerance in sensitized mice require CD1d reactive NKT cells. Methods: To determine whether NKT cells were required for ACAID induction in presensitized mice, NKT-deficient (Ja281 KO or CD1d KO) or wild type control mice were given an a.c. inoculation of OVA seven days after they were immunized with OVA in CFA subcutaneously (s.c.). To test whether ACAID was generated, the mice were given OVA-pulsed PECs intradermally in the ear pinnae one week later and ear swelling was measured. To demonstrate the importance of CD1d-NKT cell signaling, presensitized wild-type mice were given anti-CD1d mAb followed by a.c. inoculation of OVA and seven days later tested for OVA-specific DTH. Results: Sensitized wild type mice that received an a.c. inoculation of OVA a week later showed reduced ear swelling to sensitized-only mice. Mice that lacked CD1d reactive NKT cells (Ja281 KO mice or CD1d KO mice), or that were treated with anti-CD1d mAb expressed DTH responses regardless of whether they received an a.c. inoculation of the antigen or not. Conclusion: CD1d reactive NKT cells and signals from CD1d into NKT cells are required for the induction of tolerance in previously sensitized mice. Understanding mechanisms that regulate immune effector mechanisms in sensitized individuals and induce lasting tolerance may lead to therapeutic approaches for treatment of autoimmune diseases.

Keywords: 301 ACAID • 433 immune tolerance/privilege • 340 cell-cell communication