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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References
Babcock GF, Taylor AF, Hynd BA, Sramkoski RM, Alexander JW . Flow cytometric analysis of lymphocyte subset phenotypes comparing normal children and adults Diagn Clin Immunol 1987 5: 175–179
Callahan JE, Kappler JW, Marrack P . Unexpected expansions of CD8-bearing cells in old mice J Immunol 1993 151: 6657–6669
Rea IM, Stewart M, Campbell P, Alexander HD, Crockard AD, Morris TC . Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor in old and very old age Gerontology 1996 42: 69–78
Miller RA . Age-related changes in T cell surface markers: a longitudinal analysis in genetically heterogeneous mice Mech Ageing Dev 1997 96: 181–196
Mainali ES, McMurray DN . Protein deficiency induces alterations in the distribution of T-cell subsets in experimental pulmonary tuberculosis Infect Immun 1998 66: 927–931
Buchmeier MJ, Welsh RM, Dutko FJ, Oldstone MB . The virology and immunobiology of lymphocytic choriomeningitis virus infection Adv Immunol 1980 30: 275–331
Tripp RA, Hou S, McMickle A, Houston J, Doherty PC . Recruitment and proliferation of CD8+ T cells in respiratory virus infections J Immunol 1995 154: 6013–6021
Callan MF, Steven N, Krausa P et al. Large clonal expansions of CD8+ T cells in acute infectious mononucleosis Nat Med 1996 2: 906–911
Zhang ZL, Constantinou D, Mandel TE, Georgiou HM . Lymphocyte subsets in thymus and peripheral lymphoid tissues of aging and diabetic NOD mice Autoimmunity 1994 17: 41–48
Lee WH, Woodward BD . The CD4/CD8 ratio in the blood does not reflect the response of this index in secondary lymphoid organs of weanling mice in models of protein-energy malnutrition known to depress thymus-dependent immunity J Nutr 1996 126: 849–859
Falkenbach A, Sedlmeyer A . Travel to sunny countries is associated with changes in immunological parameters Photodermatol Photoimmunol Photomed 1997 13: 139–142
Kraal G, Weissman IL, Butcher EC . Genetic control of T-cell subset representation in inbred mice Immunogenetics 1983 18: 585–592
Amadori A, Zamarchi R, De Silvestro G et al. Genetic control of the CD4/CD8 T-cell ratio in humans Nat Med 1995 1: 1279–1283
Sim BC, Aftahi N, Reilly C et al. Thymic skewing of the CD4/CD8 ratio maps with the T-cell receptor alpha-chain locus Curr Biol 1998 8: 701–704
Antoniou AN, Elliott J, Rosmarakis E, Dyson PJ . MHC class II Ab diabetogenic residue 57 Asp/non-Asp dimorphism influences T-cell recognition and selection Immunogenetics 1998 47: 218–225
Robey E, Chang D, Itano A et al. An activated form of Notch influences the choice between CD4 and CD8 T cell lineages Cell 1996 87: 483–492
Gabor MJ, Scollay R, Godfrey DI . Thymic T cell export is not influenced by the peripheral T cell pool Eur J Immunol 1997 27: 2986–2993
Lander ES, Botstein D . Mapping mendelian factors underlying quantitative traits using RFLP linkage maps Genetics 1989 121: 185–199
Morel L, Mohan C, Schiffenbauer J et al. Multiplex inheritance of component phenotypes in a murine model of lupus Mamm Genome 1999 10: 176–181
Wu JM, Longmate JA, Adamus G, Hargrave PA, Wakeland EK . Interval mapping of quantitative trait loci controlling humoral immunity to exogenous antigens: Evidence that non-MHC immune response genes may also influence susceptibility to autoimmunity J Immunol 1996 157: 2498–2505
Morel L, Tian X-H, Croker BP, Wakeland EK . Epistatic modifiers of autoimmunity in a murine model of lupus nephritis Immunity 1999 11: 131–139
Lander ES, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results Nat Genet 1995 11: 241–247
Deftos ML, He YW, Ojala EW, Bevan MJ . Correlating notch signaling with thymocyte maturation Immunity 1998 9: 777–786
Linette GP, Grusby MJ, Hedrick SM, Hansen TH, Glimcher LH, Korsmeyer SJ . Bcl-2 is upregulated at the CD4+ CD8+ stage during positive selection and promotes thymocyte differentiation at several control points Immunity 1994 1: 197–205
Yu X, Fournier S, Allison JP, Sharpe AH, Hodes RJ . The role of B7 costimulation in CD4/CD8 T cell homeostasis J Immunol 2000 164: 3543–3553
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The authors would like to thank Ms Kushnir and Gajendra Tulsian for their help with animal care.
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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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DOI: https://doi.org/10.1038/sj.gene.6363819
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