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Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2

Abstract

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.

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Acknowledgements

The authors would like to thank Ms Kushnir and Gajendra Tulsian for their help with animal care.

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Correspondence to E K Wakeland.

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This work was supported by NIH Grants Al-17966, Al-17134, Al-18785, and Al-22295.

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Myrick, C., DiGuisto, R., DeWolfe, J. et al. Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2. Genes Immun 3, 144–150 (2002). https://doi.org/10.1038/sj.gene.6363819

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