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 from NOD mice display a proliferative unresponsiveness on stimulation through the T-cell receptor/CD3 complex. Interleukin 4 reverses NOD T-cell unresponsiveness in vitro and prevents the onset of diabetes in vivo, suggesting a causal relationship between the T-cell unresponsiveness and diabetes susceptibility in NOD mice. Both quantitative trait loci analysis of BXD recombinant inbred mice and linkage analysis of NOD outcross populations reveal that the control of NOD thymic T-cell proliferative unresponsiveness genetically maps to a central region on mouse chromosome 11, which includes the beta-chemokine gene family. This finding raises the possibility that a beta-chemokine(s) may regulate T-cell unresponsiveness as well as diabetes susceptibility in NOD mice.
Gill
B M
BM
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Jaramillo
A
A
Ma
L
L
Laupland
K B
KB
Delovitch
T L
TL
D000818:Animals; D002874:Chromosome Mapping; D016207:Cytokines / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D015847:Interleukin-4