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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 144-150 |
| Number of pages | 7 |
| Journal | Genes and Immunity |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 2002 |
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Keywords
- CD4 T cell subsets
- CD8 T cell subsets
- Epistasis
- Genome scan
- Quantitative trait loci
- T cells
ASJC Scopus subject areas
- Genetics(clinical)
- Immunology
- Genetics
Cite this
Linkage analysis of variations in CD4 : CD8 T cell subsets between C57BL/6 and DBA/2. / Myrick, C.; DiGuisto, R.; DeWolfe, J.; Bowen, E.; Kappler, J.; Marrack, P.; Wakeland, Edward K.
In: Genes and Immunity, Vol. 3, No. 3, 05.2002, p. 144-150.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Linkage analysis of variations in CD4
T2 - CD8 T cell subsets between C57BL/6 and DBA/2
AU - Myrick, C.
AU - DiGuisto, R.
AU - DeWolfe, J.
AU - Bowen, E.
AU - Kappler, J.
AU - Marrack, P.
AU - Wakeland, Edward K.
PY - 2002/5
Y1 - 2002/5
N2 - 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.
AB - 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.
KW - CD4 T cell subsets
KW - CD8 T cell subsets
KW - Epistasis
KW - Genome scan
KW - Quantitative trait loci
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=0036562558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036562558&partnerID=8YFLogxK
U2 - 10.1038/sj.gene.6363819
DO - 10.1038/sj.gene.6363819
M3 - Article
C2 - 12070778
AN - SCOPUS:0036562558
VL - 3
SP - 144
EP - 150
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 3
ER -