PMID:12707343

Citation	Ara, T, Itoi, M, Kawabata, K, Egawa, T, Tokoyoda, K, Sugiyama, T, Fujii, N, Amagai, T and Nagasawa, T (2003) A role of CXC chemokine ligand 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its receptor CXCR4 in fetal and adult T cell development in vivo. J. Immunol. 170:4649-55
Abstract	The functions of a chemokine CXC chemokine ligand (CXCL) 12/stromal cell-derived factor-1/pre-B cell growth stimulating factor and its physiologic receptor CXCR4 in T cell development are controversial. In this study, we have genetically further characterized their roles in fetal and adult T cell development using mutant and chimeric mice. In CXCL12(-/-) or CXCR4(-/-) embryos on a C57BL/6 background, accumulation of T cell progenitors in the outer mesenchymal layer of the thymus anlage during initial colonization of the fetal thymus was comparable with that seen in wild-type embryos. However, the expansion of CD3(-)CD4(-)CD8(-) triple-negative T cell precursors at the CD44(-)CD25(+) and CD44(-)CD25(-) stages, and CD4(+)CD8(+) double-positive thymocytes was affected during embryogenesis in these mutants. In radiation chimeras competitively repopulated with CXCR4(-/-) fetal liver cells, the reduction in donor-derived thymocytes compared with wild-type chimeras was much more severe than the reduction in donor-derived myeloid lineage cells in bone marrow. Triple negative CD44(+)CD25(+) T cell precursors exhibited survival response to CXCL12 in the presence of stem cell factor as well as migratory response to CXCL12. Thus, it may be that CXCL12 and CXCR4 are involved in the expansion of T cell precursors in both fetal and adult thymus in vivo. Finally, enforced expression of bcl-2 did not rescue impaired T cell development in CXCR4(-/-) embryos or impaired reconstitution of CXCR4(-/-) thymocytes in competitively repopulated mice, suggesting that defects in T cell development caused by CXCR4 mutation are not caused by reduced expression of bcl-2.
Links	PubMed
Keywords	Aging/genetics; Aging/immunology; Animals; B-Lymphocyte Subsets/immunology; B-Lymphocyte Subsets/metabolism; B-Lymphocyte Subsets/pathology; Bone Marrow Cells/pathology; Bone Marrow Transplantation; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Division/genetics; Cell Division/immunology; Cell Movement/immunology; Cell Survival/immunology; Cells, Cultured; Chemokine CXCL12; Chemokines, CXC/deficiency; Chemokines, CXC/genetics; Chemokines, CXC/physiology; Embryonic and Fetal Development/genetics; Embryonic and Fetal Development/immunology; Fetal Tissue Transplantation/immunology; Fetal Tissue Transplantation/pathology; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/immunology; Hematopoietic Stem Cells/metabolism; Hematopoietic Stem Cells/pathology; Liver Transplantation/immunology; Liver Transplantation/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mutation; Proto-Oncogene Proteins c-bcl-2/biosynthesis; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/physiology; Radiation Chimera/genetics; Radiation Chimera/immunology; Receptors, CXCR4/deficiency; Receptors, CXCR4/genetics; Receptors, CXCR4/physiology; T-Lymphocyte Subsets/cytology; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; T-Lymphocyte Subsets/pathology; Thymus Gland/cytology; Thymus Gland/embryology; Thymus Gland/immunology; Thymus Gland/metabolism
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