A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity

摘要: Peripheral immunological tolerance is traditionally explained by mechanisms for deletion or inactivation of autoreactive T cell clones. Using an autoimmune disease model combining transgenic mice expressing a well-defined antigen, influenza hemagglutinin (HA), on islet beta cells (Ins-HA), and receptor transgene (TCR-HNT) specific class II-restricted HA peptide, we demonstrate that the conventional assumptions do not apply to this in vivo situation. Double displayed either resistance susceptibility spontaneous disease, depending genetic contributions from two common inbred mouse strains, BALB/c B10.D2. Functional studies CD4+ resistant showed that, contrary expectations, neither clonal anergy, deletion, nor desensitization was induced; rather, there non-MHC-encoded predisposition toward differentiation nonpathogenic effector (Th2 versus Th1) phenotype. double evidence prior activation suggesting may be actively suppressed Th2 cells. These findings shed light functional aspects genetically determined autoimmunity, should lead new therapeutic approaches aimed at controlling vivo.