Soluble Peptide Treatment Reverses CD8 T Cell-Induced Disease in a Mouse Model of Spontaneous Tissue-Selective Autoimmunity

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Title: Soluble Peptide Treatment Reverses CD8 T Cell-Induced Disease in a Mouse Model of Spontaneous Tissue-Selective Autoimmunity
Author: Paek, So Yeon
Abstract: Autoimmunity is a complex process that involves recognition of self antigens by autoreactive T cells or tissue targeting by autoantibodies produced by B cells . Specific molecular targets have been identified in several autoimmune diseases but remain unknown in many others . Transgenic (Tg ) mice have been utilized to express model antigens that can be recognized by T cells or by autoantibodies . To identify mechanisms by which CD8+ autoreactive T cells cause inflammation , we generated a double transgenic (DTg ) murine model of autoimmunity by crossing K14 -sOVA mice , which express soluble chicken ovalbumin (OVA ) , with OT -1 mice , whose CD8 T cells express V2 /V5 regions of the T cell receptor that are specific for SIINFEKL peptide (OVA 257 -264 ) in association with class I MHC molecules . The K14 -SOVA /OT -1 ( #5 and #17 ) DTg mice develop normally , except that they undergo a destructive process that selectively targets the external pinnae in the first 6 days of life . The purpose of this study was to elucidate the mechanism and attempt to obviate the resulting tissue -specific destruction . By light microscopy , the ear bud area displayed an intense inflammatory infiltrate of V2 /V5+CD8+ OT -1 cells when characterized by FACS . Administration of the TCR -recognized SIINFEKL peptide i .v . to pregnant F1 mice on days E16 and E18 in utero and i .p . to newborn pups on days 2 and 4 prevented the inflammatory response and resulted in development of normal -looking ears in 100 % of pups . Treatment with the SIINFEKL peptide was shown to down -regulate the CD8 coreceptor and activate T -cells to differentiate into memory T -cells . This model can inform us about mechanisms of peripheral tolerance and potential therapies for autoimmune diseases in which specific molecular targets are known .
URI: http : / /hdl .handle .net /2152 .5 /927
Date: 2011-10-25

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Soluble Peptide Treatment Reverses CD8 T Cell-Induced Disease in a Mouse Model of Spontaneous Tissue-Selective Autoimmunity. The University of Texas Southwestern Medical Center at Dallas. Available electronically from http : / /hdl .handle .net /2152 .5 /927 .

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