CD28–B7 costimulation: a critical role for initiation and development of experimental autoimmune neuritis in C57BL/6 mice

Abstract

CD28 provides a critical costimulatory signal for antigen-specific T cell activation. Because CD28 is an important factor in the development of autoimmune diseases, we investigated its role in T cell-mediated experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome in humans. CD28-deficient mutant (CD28 −/−) C57BL/6 mice and corresponding wild-type mice were immunized with P0 peptide 180–199, a purified component of peripheral nerve myelin, and Freund’s complete adjuvant. As a result, all wild-type mice developed severe EAN, in contrast, none of the CD28 −/− mice manifested clinical signs of disease. Additionally, CD28 −/− mice had fewer IL-12 producing cells in sciatic nerve sections and fewer IFN-γ secreting splenic cells than wild-type mice on day 24 post immunization, i.e., at the peak of clinical EAN. At that time point, CD28 −/− mice had milder infiltration of such inflammatory cells as macrophages, CD4 + T cells and monocytes into sciatic nerve tissues and less demyelination than wild-type mice. Moreover, the CD28-deficiency led to reduced production of specific anti-P0 peptide 180–199 antibodies compared with wild-type mice. Evidently, CD28 is required for interaction with B7 to regulate the activation of T and B cells that initiates development of EAN.