Antigen-Specific Immune Decoys Intercept and Exhaust Autoimmunity to Prevent Disease

Abstract

Relapsing-remitting patterns of many autoimmune diseases such as multiple sclerosis (MS) are perpetuated by a recurring circuit of adaptive immune cells that amplify in secondary lympho id organs (SLOs) and traffic to compartments where antigen is abundant to elicit damage. Some of the most effective immunotherapies impede the migration of immune cells through this circuit, however, broadly suppressing immune cell migration can introduce life-threatening risks for patients. We developed antigen-specific immune decoys (ASIDs) to mimic tissues targeted in autoimmunity and selectively intercept autoimmune cells to preserve host tissue. Using Experimental Autoimmune Encephalomyelitis (EAE) as a model, we conjugated autoantige n PLP139-151 to a microporous collagen scaffold. By subcutaneously implanting ASIDs after induction but prior to the onset of symptoms, mice were protected from paralysis. ASID impla nts were rich with autoimmune cells, however, reactivity to cognate antigen was substantia lly diminished and apoptosis was prevalent. ASID-implanted mice consistently exhibited engorged spleens when disease normally peaked. In addition, splenocyte antigen-presenting cells were highly activated in response to PLP rechallenge, but CD3+ and CD19+ effector subsets were significantly decreased, suggesting exhaustion. ASID-implanted mice never developed EAE relapse symptoms even though the ASID material had long since degraded, suggesting exhausted autoimmune cells did not recover functionality. Together, data suggested ASIDs were able to sequester and exhaust immune cells in an antigen-specific fashion, thus offering a compelling approach to inhibit the migration circuit underlying autoimmunity.