Adhesion of Thymocytes to the Thymic Epithelial Cells and Participation of Neyropilin-1 and Plexin A1 in the Adhesion

Abstract

Thymic epithelial cells play not only an important structural role, but also create the microenvironment necessary for the maturation and differentiation of thymocytes. One of the stages of maturation of thymocytes is their adhesion to the epithelial cells of the thymus, the mechanism of which has not been sufficiently studied. The goal of the study was investigation of the interaction of mouse thymocytes with cortical cTEC1-2 and the medullary mTEC3-10 thymic epithelial cell lines, namely, the dynamics of the adhesion, apoptosis, and population composition, as well as the expression of the neuropilin-1 (Nrp-1) and plexin A1 receptors (PlexA1) among adherent, nonadherent, and control cells cultured without epithelium. The maximal adhesion index was observed for a 30-min cocultivation; after this time, the index decreased. The main population of adherent cells consisted from immature CD4⁺CD8⁺ lymphocytes, and the relative content of mature CD4⁺ and CD8⁺ thymocytes was lower than in the control. We have shown for the first time that, even at short cocultivation periods (30 and 120 min), an increase in the content of thymocytes at the early apoptosis phase was observed among the population of adherent cells. For the first time, data have been obtained demonstrating the participation of Nrp-1 and PlexA1 in the process of thymocyte adhesion to mouse thymic epithelial cells as independent molecules in the absence of their semaphorin 3A ligand. It was shown that the expression of Nrp-1 on the surface of adherent thymocytes was significantly reduced during the adhesion process compared to the control, and the expression of PlexA1 increased. Preincubation of thymocytes with antibodies to Nrp-1 increased their adhesion to epithelial cells. The data obtained contribute to a better understanding of intercellular relationships in the thymus gland.