Neutrophils that infiltrate the central nervous system regulate T cell responses

Regulation of inflammatory responses is critical to progression of organ-specific autoimmune disease. Although many candidate cell types have been identified, immunoregulatory activity has rarely been directly assayed and never from the CNS. We have analyzed the regulatory capability of Gr-1(high) neutrophils isolated from the CNS of mice with experimental autoimmune encephalomyelitis. Proportions of neutrophils were markedly increased in the CNS of IFN-gamma-deficient mice. Strikingly, CNS-derived neutrophils, whether or not they derived from IFN-gamma-deficient mice, were potent suppressors of T cell responses to myelin or adjuvant Ags. Neutrophil suppressor activity was absolutely dependent on IFN-gamma production by target T cells, and suppression was abrogated by blocking NO synthase. These data identify an immunoregulatory capacity for neutrophils, and indicate that interplay between IFN-gamma, NO, and activated Gr-1(high) neutrophils within the target organ determines the outcome of inflammatory and potentially autoimmune T cell responses.