Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2.
The ratio of CD4 T cells to CD8 T cells (CD4:CD8 ratio) varies over two-fold between C57BL/6 and DBA/2 mice for both T cell precursors in the thymus and mature T cells in the periphery. Correlation analysis of the CD4:CD8 ratio in thymic precursors vs peripheral T cells in F2 and backcross mice found that thymic precursor ratios are inherited independently from those in the periphery, indicating that the CD4:CD8 ratios in these populations are affected by distinct genetic mechanisms. A genome scan of progeny in the phenotypic extremes identified three quantitative trait loci (QTLs). Trmq1 (for T cell ratio modifier QTL 1) was detected in the telomeric end of c6 (peak marker D6Mit15 at 74 cM) and had a maximum LOD score of 4.6. Trmq2, in the telomeric half of c2, peaked at D2MIT483 and had a maximum LOD score of 3.41. Both of these QTLs impacted the CD4:CD8 ratios in peripheral T cells and had no impact on variation in this ratio among thymic precursors. However, heterozygosity for the H2 complex was suggestively associated (LOD score of 2.43) with increases in CD4 T cells among T cell precursors in the thymus. All of these QTLs were affected by epistatic interactions, indicating that additional modifiers in the B6 and DBA/2 genomes modulate this phenotype.
Myrick
C
C
Center for Mammalian Genetics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
DiGuisto
R
R
DeWolfe
J
J
Bowen
E
E
Kappler
J
J
Marrack
P
P
Wakeland
E K
EK
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D008040:Genetic Linkage; D008126:Lod Score; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity; D013950:Thymus Gland / Q000378:metabolism