Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11.
Age-related decline in thymic T-cell development in 22-month-old C57BL/6J X DBA/2J (BXD) recombinant inbred strains of mice was functionally and phenotypically analyzed and genetically mapped. There was a positive correlation of the concanavalin A (Con A)-induced thymocyte proliferative response with the capability of thymocytes to mature to the CD4(+)CD8(+) stage. The accumulation of CD4(-)CD8(-) stage of thymocytes in 22-month-old BXD mice was further identified to be associated with a developmental block between the CD25(-)CD44(+) and the CD25(+)CD44(+) stages. The quantitative trait loci regulating the Con A-induced thymocyte proliferative response were mapped to mouse chromosome 1, 3, and 11, nearest to 32.1 centimorgan (cM), 5.6 cM, and 18.0 cM, respectively. Our results suggest that several genetic loci regulate the intra-thymic T-cell maturation process and play an important role in determining age-related decline in thymic T-cell development.
Hsu
Hui-Chen
HC
Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, 701 South 19th Street, LHRB 473, Birmingham, AL 35294-0007, USA. huichen.hsu@cccc.uab.edu
Mountz
John D
JD
Williams
Robert W
RW
Shelton
Brent J
BJ
Yang
Ping-Ar
PA
Matsuki
Yasunori
Y
Xu
Xin
X
Dodd
Christopher H
CH
Li
Lina
L
Geiger
Hartmut
H
Zhang
Huang-Ge
HG
Van Zant
Gary
G
D000375:Aging / Q000235:genetics* / Q000276:immunology; D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003208:Concanavalin A / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology*
D015415:Biomarkers; D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2; D003208:Concanavalin A