Characterization of Vascular Adhesion Molecules that may Facilitate Progenitor Homing in the Post‐natal Mouse Thymus

Abstract

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.

A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus

“…In contrast, progenitor homing to the BM depended almost exclusively on ␣4 integrins. ICAM-1 and VCAM-1, the counterreceptors for ␣L␤2 and ␣4␤1, respectively, are expressed in thymus corticomedullary vessels, where the entry of lymphoid progenitors is thought to occur (10,38). Given the additive effect of combined inhibition of these pathways, our results suggest that both ␣L␤2͞ICAM-1 and ␣4␤1͞VCAM-1 can mediate arrest of rolling progenitors in thymus microvessels.…”

“…5A). Thymic endothelial cells express ICAM-1 and VCAM-1, which function as counterreceptors for ␣L␤2 and ␣4␤1, respectively (38). Indeed, mAb inhibition of ICAM-1 or VCAM-1 reduced CLP-2 homing to the thymus by 39 Ϯ 4% and 70 Ϯ 5%, respectively.…”

T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome

“…CD62L, which was previously reported as being induced during proteinuria in nephrotic patients [18], is an early marker of T-cell commitment in bone marrow progenitors [27] and is involved in thymic homing [28]. CD62L is also expressed in circulating recent thymic emigrant and naive T cells (in which it plays a major role in lymph nodes homing), but its expression is markedly reduced in mature T cells [29].…”

Lymphocyte Trafficking

“…Expression of α 4 β 1 on thymocytes, combined with that of VCAM-1 on thymic blood vessels, make this pathway a likely mediator of progenitor rolling and adhesion in thymic post-capillary venules [81,94] . Expression of α 4 β 1 on thymocytes, combined with that of VCAM-1 on thymic blood vessels, make this pathway a likely mediator of progenitor rolling and adhesion in thymic post-capillary venules [81,94] .…”

“…Expression of α 4 β 1 on thymocytes, combined with that of VCAM-1 on thymic blood vessels, make this pathway a likely mediator of progenitor rolling and adhesion in thymic post-capillary venules [81,94] . One study has detected PNAd and ICAM-1 on thymic vessels [94] . One study has detected PNAd and ICAM-1 on thymic vessels [94] .…”