Critical Role for CXCR4 Signaling in Progenitor Localization and T Cell Differentiation in the Postnatal Thymus

• Published in: The Journal of immunology (1950) Vol. 171; no. 9; pp. 4521 - 4527
• Main Authors: Plotkin, Jason, Prockop, Susan E, Lepique, Ana, Petrie, Howard T
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.2003
• Subjects: Animals; Animals, Newborn - genetics; Animals, Newborn - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Movement - genetics; Cell Movement - immunology; Chemokine CXCL12; Chemokines, CXC - biosynthesis; Chemokines, CXC - pharmacology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Keratins - biosynthesis; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - genetics; Receptors, CXCR4 - deficiency; Receptors, CXCR4 - genetics; Receptors, CXCR4 - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Stromal Cells - immunology; Stromal Cells - metabolism; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.9.4521

T cell differentiation in the thymus depends on sequential interactions between lymphoid progenitors and stromal cells in discrete regions of the cortex. Here we show that CXCL12/CXCR4 signaling is absolutely required for proper localization of early progenitors into the cortex and thus for successful steady state differentiation. All early progenitors in the thymus express CXCR4, and its ligand (CXCL12) is expressed only by stromal cells in the cortex, where early progenitors are found. Early progenitors migrate in response to CXCL12 in vitro, while thymus-specific deletion of CXCR4 in vivo results in failed cortical localization and developmental arrest. These findings indicate a crucial and nonredundant role for CXCR4 in facilitating localization of early lymphoid progenitors to tissue regions of the thymus, where lineage commitment and proliferation are controlled.