Characterization of vascular adhesion molecules that may facilitate progenitor homing in the post-natal mouse thymus.
T cell progenitors derive from the bone marrow but must migrate via bloodstream to the thymus in order to differentiate. The mechanism by which the thymus recruits progenitors from the blood is unknown. It is known, however, that there are receptive and refractory periods for progenitor recruitment and that when cells are imported, they enter the thymus through post-capillary venules. Therefore, recruitment is an active process temporally and spatially regulated. In order to characterize the mechanism of recruitment, we evaluated vascular signals known to regulate leukocyte extravasation, with respect to their intrathymic location and temporal fluctuations. We find that CD34, MECA79, VCAM-1, ICAM-1 and VAP-1 are all expressed in thymic blood vessels. MECA79 and VAP-1 appear to be specific for post-capillary venules, while ICAM-1 and VCAM-1 are also found on intrathymic stromal cells. MAdCAM is also expressed in the thymus, but is not associated with vascular tissues. Only MECA79 is upregulated during recruitment peaks, suggesting a role for this molecule in the periodicity of recruitment. Together, these studies reveal potential roles for L-selectin ligands, VCAM-1, ICAM-1 and VAP-1 in progenitor recruitment to the thymus, and implicate the presence of other periodic signals, such as chemokines and cytokines, that cooperate to execute this essential function.
Memorial Sloan-Kettering Cancer Center, Box 341, 1275 York Avenue, New York, NY 10021, USA.
Ana Paula
AP
Lepique
Sharina
S
Palencia
Heikki
H
Irjala
Howard T
HT
Petrie
D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins / Q000096:biosynthesis; D017154:Stromal Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000098:blood supply* / Q000276:immunology* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014699:Venules / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)