期刊
JOURNAL OF IMMUNOLOGY
卷 167, 期 2, 页码 1112-1117出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.167.2.1112
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资金
- NIDDK NIH HHS [DK 57644, DK 50824] Funding Source: Medline
Nonobese diabetic (NOD) mice develop spontaneous autoimmune diabetes that involves participation of both CD4(+) and CD8(+) T cells. Previous studies have demonstrated spontaneous reactivity to self-Ags within the CD4+ T cell compartment in this strain. Whether CDS' T cells in NOD mice achieve and maintain tolerance to self-Ags has not previously been evaluated. To investigate this issue, we have assessed the extent of tolerance to a model pancreatic Ag, the hemagglutinin (HA) molecule of influenza virus, that is transgenically expressed by pancreatic islet beta cells in InsHA mice. Previous studies have demonstrated that BALB/c and MOM mice that express this transgene exhibit tolerance of HA and retain only low-avidity CD8(+) T cells specific for the dominant peptide epitope of HA. In this study, we present data that demonstrate a deficiency in peripheral tolerance within the CDS' T cell repertoire of NOD-InsHA mice. CD8(+) T cells can be obtained from NOD-InsHA mice that exhibit high avidity for HA, as measured by tetramer (K(d)HA) binding and dose titration analysis. Significantly, these autoreactive CD8(+) T cells can cause diabetes very rapidly upon adoptive transfer into NOD-InsHA recipient mice. The data presented demonstrate a retention in the repertoire of CD8(+) T cells with high avidity for islet Ags that could contribute to autoimmune diabetes in NOD mice.
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