Tracking of individual autoreactive and regulatory T cells in Aire deficient TCR "mini" Foxp3-GFP mice (48.16)

Abstract

Abstract The presentation of tissue specific antigens (TSA) in the thymus is crucial in developing tolerant T cells and the lack thereof, leads to the development of autoimmunity (AI). Peripherally, autoreactive T cells (TA cell) that escape central tolerance can be controlled by FoxP3+ (TRcells). Mice deficient of the Aire gene lack Aire dependent TSA expression and develop organ-specific AI. It has been postulated that in the absence of Aire the diversity of TRcells positively selected is compromised. We propose to examine the effect of Aire on the T cell repertoire at the level of a single T cell clone, using an in vivo model (Aire-/-TCRminiFoxp3GFP mice) where Aire deficient mice express polyclonal, but miniature TCR repertoires. The T cells have a narrow αβ TCR repertoire composed of one transgenic TCR Vβ14+ chain and various TCRα chains produced by the rearrangements of the transgenic Vα2-Jα26,Jα2 mini-locus. The sequence of the CDR3 regions can be used as "tags" to follow the expansion of T cells and GFP driven by the FoxP3 promoter labels all TRcells. We show that irrespective of the mini repertoire, these mice develop multi-organ AI characterized by circulating autoantibodies and organ infiltrates. Analysis of individual TA and TRcell infiltrating organs show non-overlapping repertoires with the expansion of specific T cells. Further research will reveal if these clones are the tissue specific "culprits" responsible for this AI.