A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus.
Homing of bone marrow (BM)-derived progenitors to the thymus is essential for T cell development. We have previously reported that two subpopulations of common lymphoid progenitors, CLP-1 and CLP-2, coexist in the BM and give rise to lymphocytes. We demonstrate that CLP-2 migrate to the thymus more efficiently than any other BM-derived progenitors. Short-term adoptive transfer experiments revealed that CLP-2 homing involves P-selectin/P-selectin glycoprotein ligand 1 interactions, pertussis toxin-sensitive chemoattractant signaling by CC chemokine ligand 25 through CC chemokine receptor 9, and binding of the integrins alpha4beta1 and alphaLbeta2 to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Preferential thymus-tropism of CLP-2 correlated with higher chemokine receptor 9 expression than on other BM progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade.
Scimone
M Lucila
ML
The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Aifantis
Iannis
I
Apostolou
Irina
I
von Boehmer
Harald
H
von Andrian
Ulrich H
UH
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology; D002633:Chemotaxis / Q000502:physiology*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D016023:Integrins; D019007:P-Selectin; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D051960:GTP-Binding Protein alpha Subunit, Gi2