Bovine gamma delta T cells express high levels of functional peripheral lymph node homing receptor (L-selectin).

Abstract

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-selectin, for example, directs the migration of lymphocytes into peripheral lymph nodes (PLN). Since bovine gamma delta 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 gamma delta T cells expressed L-selectin at levels higher (2- to 5-fold) than alpha beta T cells and B cells. Furthermore, gamma delta 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 ex vivo binding assay. In contrast to this primary adhesive event, we directly demonstrate that gamma delta T cells in vivo do not appreciably extravasate from the blood into the parenchyma of lymph nodes. Since the lack of functional L-selectin expression could not account for the inability of gamma delta T cells to enter PLN, we tested for other differences between gamma delta 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 transendothelial migration. We found that gamma delta and alpha beta 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 gamma delta T cells and was down-regulated at a slower rate compared with alpha beta T cells. However, the expression levels of CD44 and CD18 on gamma delta and alpha beta T cells were found to be equivalent. This study is the first to demonstrate for lymphocytes that the expression of L-selectin alone does not predict a PLN homing capacity. Our results suggest that the gamma delta T cells' reduced ability to enter PLN may be due to inefficient down-regulation of L-selectin compared with non-gamma delta lymphocytes, thus potentially disrupting the dynamics of the extravasation event.