Lymphocyte migration from the blood into specific tissues Is directed by their expression of adhesion molecules referred to as homing receptors. The homing receptor L-selectln, for example, directs the migration of lymphocytes into peripheral lymph nodes (PLN). Since bovine γδ T cells, a major lymphocyte subset in peripheral blood (25-50%), represent only a minor subset in PLN, we examined whether these cells lack expression or function of L-selectin. We found that bovine γδ T cells expressed L-selectln at levels higher (2- to 5-fold) than αβ T cells and B cells. Furthermore, γδ T cells accumulated along the vascular wall of venules that support lymphocyte extravasation into PLN (MECA-79+ venules) in vivo and bound mouse PLN high endothelial cell venules in an In vivo binding assay. In contrast to this primary adhesive event, we directly demonstrate that γδ T cells in vivo do not appreciably extravasate from the blood into the parenchyma of lymph nodes. Since the lack of functional L-selectln expression could not account for the inability of γδ T cells to enter PLN, we tested for other differences between γδ T cells and PLN homing lymphocytes related to the processes following primary adhesion; for instance, the down-regulation of L-selectin expression following short-term activation and the expression of accessory adhesion molecules necessary for transendothellal migration. We found that γδ and αβ T cells demonstrate differential down-regulation of L-selectin after PMA activation. Kinetic analysis revealed that, at all time points after PMA treatment, L-selectin expression remained significantly higher on γδ T cells and was down-regulated at a slower rate compared with αβ T cells. However, the expression levels of CD44 and CD18 on γδ and αβ T cells were found to be equivalent. This study Is the first to demonstrate for lymphocytes that the expression of L-selectln alone does not predict a PLN homing capacity. Our results suggest that the γδ T cells' reduced ability to enter PLN may be due to inefficient down-regulation of L-selectln compared with non-γδ lymphocytes, thus potentially disrupting the dynamics of the extravasation event.
Bibliographical noteFunding Information:
The authors wish to acknowledge Gayte Watts and Sandy Kurk for expert technical assistance, Kathryn Jutila for antibody and hybridoma production, Andy Blixt for photomicroscopy, and Dana Hoover for manuscript preparation. These studies were supported in part by grants from the USDA (CSRS9001666), Pardee Foundation, and the Montana Agriculture Experiment Station (J2183).
Copyright 2010 Elsevier B.V., All rights reserved.
- High endothelial cell venule
- Homing receptor
- Peripheral lymph node