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.
It has been repeatedly shown that a subset of CD4+ T cells that constitutively express CD25 on their surface plays a role in the maintenance of 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-prone mice as they reached 7 to 8 months of age. However, mice with an autoimmune background differed 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 contributes to a susceptibility to develop spontaneous lupus disease.
Wu
H Y
HY
The Infection and Immunity Research Group, Franklin-Wilkins Building, King's College London, London, UK. hwu@rics.bwh.harvard.edu
Staines
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NA
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006657:Histones / Q000494:pharmacology*; D007108:Immune Tolerance / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017634:Self Tolerance; D013045:Species Specificity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D001324:Autoantigens; D006657:Histones; D015375:Receptors, Interleukin-2