Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11

Hui Chen Hsu; John D. Mountz; Robert W. Williams; Brent J. Shelton; Ping Ar Yang; Yasunori Matsuki; Xin Xu; Christopher H. Dodd; Lina Li; Hartmut Geiger; Huang Ge Zhang; Gary Van Zant

doi:10.1016/S0047-6374(02)00004-0

Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11

Hui Chen Hsu
, John D. Mountz
, Robert W. Williams
, Brent J. Shelton
, Ping Ar Yang
, Yasunori Matsuki
, Xin Xu
, Christopher H. Dodd
, Lina Li
, Hartmut Geiger
, Huang Ge Zhang
, Gary Van Zant

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1145-1158
Number of pages	14
Journal	Mechanisms of Ageing and Development
Volume	123
Issue number	8
DOIs	https://doi.org/10.1016/S0047-6374(02)00004-0
State	Published - Apr 30 2002

Bibliographical note

Funding Information:
We thank Dr. T. Rogers and Mr. M. Spell of the FACS Core Facility at UAB for operating the FACS. We also thank Dr. F. Hunter and Ms. D. Downs for critical review of the manuscript and Ms. Linda Flurry for excellent secretary work. This work is supported by NIH grants R01 AG 16653, N01 AR 6-2224, and CA 20408, and a Birmingham VAMC Merit Review Grant. Hui-Chen Hsu is a recipient of a grant from the Center for Aging at the University of Alabama at Birmingham. Huang-Ge Zhang is a recipient of Arthritis Foundation Investigator Award. Hartmut Geiger was supported by a fellowship of the Deutsch e Akademie der Naturforscher Leopoldina funded by the Bundesministerium für Bildung und Forschung.

Funding

We thank Dr. T. Rogers and Mr. M. Spell of the FACS Core Facility at UAB for operating the FACS. We also thank Dr. F. Hunter and Ms. D. Downs for critical review of the manuscript and Ms. Linda Flurry for excellent secretary work. This work is supported by NIH grants R01 AG 16653, N01 AR 6-2224, and CA 20408, and a Birmingham VAMC Merit Review Grant. Hui-Chen Hsu is a recipient of a grant from the Center for Aging at the University of Alabama at Birmingham. Huang-Ge Zhang is a recipient of Arthritis Foundation Investigator Award. Hartmut Geiger was supported by a fellowship of the Deutsch e Akademie der Naturforscher Leopoldina funded by the Bundesministerium für Bildung und Forschung.

Funders	Funder number
Center for Health and Aging
National Institutes of Health (NIH)	R01 AG 16653, N01 AR 6-2224
National Childhood Cancer Registry – National Cancer Institute	R01CA020408
Bundesministerium für Bildung und Forschung
Deutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der Wissenschaften

Keywords

Aging
Quantitative trait loci
Recombinant inbred mice
T cells
Thymic involution

ASJC Scopus subject areas

Aging
Developmental Biology

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10.1016/S0047-6374(02)00004-0

Cite this

Hsu, H. C., Mountz, J. D., Williams, R. W., Shelton, B. J., Yang, P. A., Matsuki, Y., Xu, X., Dodd, C. H., Li, L., Geiger, H., Zhang, H. G., & Van Zant, G. (2002). Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11. Mechanisms of Ageing and Development, 123(8), 1145-1158. https://doi.org/10.1016/S0047-6374(02)00004-0

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title = "Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11",

abstract = "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.",

keywords = "Aging, Quantitative trait loci, Recombinant inbred mice, T cells, Thymic involution",

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note = "Funding Information: We thank Dr. T. Rogers and Mr. M. Spell of the FACS Core Facility at UAB for operating the FACS. We also thank Dr. F. Hunter and Ms. D. Downs for critical review of the manuscript and Ms. Linda Flurry for excellent secretary work. This work is supported by NIH grants R01 AG 16653, N01 AR 6-2224, and CA 20408, and a Birmingham VAMC Merit Review Grant. Hui-Chen Hsu is a recipient of a grant from the Center for Aging at the University of Alabama at Birmingham. Huang-Ge Zhang is a recipient of Arthritis Foundation Investigator Award. Hartmut Geiger was supported by a fellowship of the Deutsch e Akademie der Naturforscher Leopoldina funded by the Bundesministerium f{\"u}r Bildung und Forschung.",

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AU - Hsu, Hui Chen

AU - Mountz, John D.

AU - Williams, Robert W.

AU - Shelton, Brent J.

AU - Yang, Ping Ar

AU - Matsuki, Yasunori

AU - Xu, Xin

AU - Dodd, Christopher H.

AU - Li, Lina

AU - Geiger, Hartmut

AU - Zhang, Huang Ge

AU - Van Zant, Gary

N1 - Funding Information: We thank Dr. T. Rogers and Mr. M. Spell of the FACS Core Facility at UAB for operating the FACS. We also thank Dr. F. Hunter and Ms. D. Downs for critical review of the manuscript and Ms. Linda Flurry for excellent secretary work. This work is supported by NIH grants R01 AG 16653, N01 AR 6-2224, and CA 20408, and a Birmingham VAMC Merit Review Grant. Hui-Chen Hsu is a recipient of a grant from the Center for Aging at the University of Alabama at Birmingham. Huang-Ge Zhang is a recipient of Arthritis Foundation Investigator Award. Hartmut Geiger was supported by a fellowship of the Deutsch e Akademie der Naturforscher Leopoldina funded by the Bundesministerium für Bildung und Forschung.

PY - 2002/4/30

Y1 - 2002/4/30

N2 - 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.

AB - 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.

KW - Aging

KW - Quantitative trait loci

KW - Recombinant inbred mice

KW - T cells

KW - Thymic involution

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UR - https://www.scopus.com/pages/publications/18444372356#tab=citedBy

U2 - 10.1016/S0047-6374(02)00004-0

DO - 10.1016/S0047-6374(02)00004-0

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AN - SCOPUS:18444372356

SN - 0047-6374

VL - 123

SP - 1145

EP - 1158

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

IS - 8

ER -

Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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