DAP-12, a Major Immunomediator, Either Promotes or Suppresses Experimental Autoimmune Uveitis (EAU) Development

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NEI	IMMUNO-22

Authors

• B.P. Vistica
• V. Montalvo-Reddin
• G. Shi
• L. Nugent
• L. Quigley
• D.W. McVicar
• I. Gery

Abstract

DAP-12 (DNAX-activating protein of 12kDa), plays a major role in the immune response by transducing a variety of activation signals. The role of DAP-12 in the etiology of pathogenic autoimmunity has been controversial by either enhancing or depressing experimental autoimmune diseases. Here, we compared DAP-12 null mice and wild type (WT) controls for their susceptibility to EAU induction and immune responsiveness. DAP-12 null mice and their WT controls were obtained from two animal facilities with low (“A”) or high (“B”) standards. The mice were immunized with the retinal antigen “IRBP” and their development of EAU was evaluated clinically and histologically. Draining lymph node cells were cultured with IRBP to measure proliferation and cytokine release. Although disease in control mice from both facilities was comparable, DAP-12 null mice from facility A were superior to their WT controls in both the severity of their ocular inflammation and the levels of proliferation and cytokines produced by their lymphocytes. In contrast, DAP-12 null mice from facility B were inferior to their controls by both parameters. Our data provide a possible resolution to the controversy concerning the role of DAP-12: deficiency in this molecule can either promote or suppress the pathogenic response depending on environment.

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