CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity A Unifying Hypothesis英文文献资料.docVIP

HindawiPublishingCorporation AutoimmuneDiseases Volume2012,ArticleID189096,16pages doi:10.1155/2012/189096 ReviewArticle CD8+T-CellDe?ciency,Epstein-BarrVirusInfection,VitaminD De?ciency,andStepstoAutoimmunity:AUnifyingHypothesis MichaelP.Pender 1,2 1 2 SchoolofMedicine,TheUniversityofQueensland,Brisbane,QLD4072,Australia DepartmentofNeurology,RoyalBrisbaneandWomen’sHospital,Brisbane,QLD4029,Australia CorrespondenceshouldbeaddressedtoMichaelP.Pender,m.pender@.au Received18August2011;Revised3October2011;Accepted16October2011 AcademicEditor:CorradoBetterle Copyright?2012MichaelP.Pender.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. CD8+T-cell de?ciency is a feature of many chronic autoimmune diseases, including multiple sclerosis,rheumatoid arthritis, systemic lupus erythematosus, Sj¨ogren’s syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn’s disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilatedcardiomyopathy,type1diabetesmellitus,Graves’disease,Hashimoto’sthyroiditis,myastheniagravis,IgAnephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases,suggestingitisgeneticallydetermined.HereitisproposedthatthisCD8+T-cellde?ciencyunderliesthedevelopment ofchronicautoimmunediseasesbyimpairingCD8+T-cellcontrolofEpstein-Barrvirus(EBV)infection,withtheresultthat EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis.Autoimmunityispostulatedtoevolveinthefollowingsteps:(1)CD8+T-cellde?ciency,(2)primaryEBVinfection, (3)decreasedCD8+T-cellcontrolofEBV,(4)i