A deficiency of CD4+ CD25+ T cells permits the development of spontaneous lupus-like disease in mice,and can be reversed by induction of mucosal tolerance to histone peptide autoantigen

Abstract

It has been repeatedly shown that a subset of CD4⁺ T cells that constitutively express CD25 on their surface plays a role in the maintenanceof self-tolerance.They may directly or indirectly affect the development of autoimmunity in susceptible mice and humans. In this study, we examine the relationship between the percentage of peripheral CD4⁺CD25⁺ T cells and the state of disease in spontaneous models of autoimmune disease. We found that both BWF1 and SNF1 mice that spontaneously develop a lupus-like disease have inherently lower percentage of the CD4⁺CD25⁺ T cells in their CD4 repertoire compared with normal Balb/c and DBA/1 mice. The percentage of CD4⁺CD25⁺ T cells was found to be increased in both normal and lupus-pronemice as they reached 7 to 8 months of age. However, mice with an autoimmune backgrounddiffered from mice on a normal background in that the number of CD4⁺CD25⁺ T cells never reached 5% of the CD4 population.The lower number of the CD4⁺CD25⁺ T cells in autoimmune mice was restored to the level seen in normal mice following administration of histone peptide H471 or OVA(323-339) peptide in the absence of adjuvant intranasally but not intradermally. As such transmucosal treatment may ameliorate disease, we conclude that a deficiency in the CD4⁺CD25⁺ T cell pool contributesto a susceptibilityto develop spontaneous lupus disease.