GENETIC-LINKAGE OF THYMIC T-CELL PROLIFERATIVE UNRESPONSIVENESS TO MOUSE CHROMOSOME-11 IN NOD MICE - A POSSIBLE ROLE FOR CHEMOKINE GENES

Thymic and peripheral T-cells hom NOD mice display a proliferative unr esponsiveness on stimulation through the T-cell receptor/CD3 complex, Interleukin 4 reverses NOD T-cell unresponsiveness in vitro and preven ts the onset of diabetes in vivo, suggesting a causal relationship bet ween the T-cell unresponsiveness and diabetes susceptibility in NOD mi ce. Both quantitative trait loci analysis of BXD recombinant inbred mi ce and linkage analysis of NOD outcross populations reveal that the co ntrol of NOD thymic T-cell proliferative unresponsiveness genetically maps to a central region on mouse chromosome 11, which includes the be ta-chemokine gene family. This finding raises the possibility that a b eta-chemokine(s) may regulate T-cell unresponsiveness as well as diabe tes susceptibility in NOD mice.