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

• Published in: Lupus 2004-03, Vol.13 (3), p.192-200
• Main Authors: Wu, H Y, Staines, N A
• Format: Article
• Language: English
• Subjects: Animals; Autoantigens - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Division - immunology; Disease Models, Animal; Female; Histones - pharmacology; Immune Tolerance - physiology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - physiopathology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, SCID; Receptors, Interleukin-2 - immunology; Self Tolerance; Species Specificity; T-Lymphocytes, Regulatory - drug effects
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1191/0961203303lu1002oa

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.