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A role for CCR9 in T lymphocyte development and migration
Shoji Uehara1, Alexander Grinberg, Joshua M Farber
1Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, and Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Journal of Immunology (Baltimore, Md. : 1950)
|March 9, 2002
Summary
Chemokine receptor CCR9 (CC chemokine receptor type 9) is crucial for T cell development and migration. CCR9 deficiency impacts T cell populations in the thymus and small intestine, affecting both alpha beta and gamma delta T lymphocytes.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Chemokine receptor CCR9 (CC chemokine receptor type 9) is expressed on T cells in the thymus and small intestine.
- CCR9 mediates chemotaxis in response to CCL25 (chemokine ligand), also known as thymus-expressed chemokine.
- Its specific role in T cell development and homing requires further investigation.
Purpose of the Study:
- To investigate the role of CCR9 in T cell development and lymphocyte populations.
- To determine the impact of CCR9 deficiency on T cell populations in the thymus and small intestine.
Main Methods:
- Gene disruption of CCR9 using homologous recombination in mice.
- Analysis of B cell and T cell development in CCR9-deficient (CCR9(-/-)) mice.
- Competitive bone marrow transplantation experiments.
- Flow cytometry analysis of T cell populations in thymus and small intestine.
Main Results:
- B cell development and thymic alphabeta-T cell development were unimpaired in adult CCR9(-/-) mice.
- CCR9(-/-) bone marrow showed reduced efficiency in repopulating the thymus of recipient mice.
- CCR9(-/-) mice exhibited increased peripheral gammadelta-T cells but reduced gammadeltaTCR(+) and CD8alphabeta(+)alphabetaTCR(+) intraepithelial lymphocytes in the small intestine.
Conclusions:
- CCR9 plays a significant, though not essential, role in regulating T lymphocyte development and/or migration.
- CCR9 influences the populations of both alphabeta and gammadelta T lymphocytes in the periphery and gut.
- These findings highlight CCR9's importance in T cell homing and immune surveillance in the gut-associated lymphoid tissues.