Defective central tolerance in Aire-deficient mice is not sufficient to induce symptomatic autoimmunity during lymphopenia-induced T cell proliferation.

Transcriptional regulator autoimmune regulator (AIRE) controls thymic negative selection but it is also expressed in secondary lymphoid organs. The relative contribution of AIRE's central and peripheral function to the maintenance of tolerance is unclear. We transferred mature lymphocytes from Aire(-/-) or wild-type donors to Aire(+/+) lymphopenic recipients, which allowed us to gauge the autoreactivity inherent in the cells originating in an Aire(-/-) thymus. In the ensuing lymphopenia-induced proliferation (LIP), the recipients of cells from Aire(-/-) showed definite T cell hyperproliferation and developed autoantibodies at a higher frequency than the recipients of wild-type cells. However, neither of the recipient groups developed clinical symptoms, and pathological tissue infiltrates were also absent. The recipients of Aire(-/-) cells showed hyperproliferation and increased accumulation of regulatory T cells (Tregs), especially in tissues susceptible to inflammation triggered by LIP. These data are consistent with the view that T cells developing in the absence of Aire are autoreactive. However, overt autoimmunity was prevented, most likely by the suppressive function of Treg cells in the Aire-sufficient recipients. Our results support the importance of the peripheral AIRE expression in the maintenance of immunological tolerance.

Variable number of pig MHC class I genes in different serologically defined haplotypes identified by a 3'-untranslated region probe.

To estimate the number of porcine class I major histocompatibility genes, a short class I cDNA probe from the 3'-untranslated region was developed to be used in restriction fragment length polymorphism analysis. Six clones isolated from a pig spleen cDNA library were sequenced from their 3'-untranslated region. Three different transcripts were identified, one probably derived from the class I PD7 locus and two showing highest homology to the PD1 and the PD14 genes, respectively. Class I typing was performed both by restriction fragment length polymorphism and serology. Segregation of class I haplotypes was followed in one three-generation family (European Wild Boar x Large White: Swedish Yorkshire) and in six two-generation families (Duroc, Yorkshire and Chester White), for a total of 266 pigs. Twenty different class I haplotypes were identified either with restriction fragment length polymorphism and/or serological typing. Furthermore, previously unpublished serological haplotypes H62, H67 and H68 were identified. Two to seven polymorphic and three monomorphic fragments were detected in different restriction fragment length polymorphism haplotypes indicating that the number of class I genes in the investigated haplotypes varies.

Restriction fragment length polymorphisms at the heat shock protein HSP70 gene(s) in pigs.

Pigs from a population consisting of eight US breeds or strains and three Chinese breeds were examined by restriction fragment length polymorphism (RFLP) analysis of the heat shock protein HSP70 gene(s). Limited polymorphisms with PstI and PvuII restriction enzymes were observed, but there were no polymorphisms with BamHI and BglI.