Dynamics of Complex Formation between Thymocytes and Thymic Medullary Epithelial Cells

Abstract

Direct cell contact is an intrinsic part of several differentiation processes. A case in point is the formation of complexes between thymic lymphocytes and stromal cells, which are essential for T-cell maturation. The objective of the present work was to gain an insight into the mechanisms underlying the formation and dissociation of such lymphostromal complexes. Using an in vitro system, we show that the number of thymocytes adhering to a thymic medullary epithelial cell line (E-5) increases with time and reaches a plateau, after which some thymocytes spontaneously detach, while the rest remain attached to epithelium. The detached and forcibly removed thymocytes were analysed for their expression of L3T4 and Ly-2 antigens. The detached thymocytes showed a markedly lowered expression of both antigens. Both of these subtypes were shown to be totally refractory to form further complexes after a first encounter with E-5 cells. We also show that, once a mean adherence level of one thymocyte per E-5 cell was reached, (a) the level of further adherence increased exponentially, and (b) during this phase, binding of thymocytes to E-5 cells occurred in clusters, indicating pre-existing polarity or contact-induced polarization of the receptors at the E-5 cell surface.

A novel thymic epithelial adhesion molecule

“…Its low molecular weight and functional independence from divalent cations, both on intact E-5 cells [15] and in purified form (Sect. 2.6), clearly indicates the uniqueness of this adhesion molecule.…”

“…The physical structure of this adhesion molecule is, to the best of our knowledge, different from any known epithelial adhesion molecule involved in lymphocyte/epithelial [ 12- 14,27,28] or even epitheliaUepithelia1 cell interactions [29], most of which are calcium dependent. Its low molecular weight and functional independence from divalent cations, both on intact E-5 cells [15] and in purified form (Sect. 2.6), clearly indicates the uniqueness of this adhesion molecule.…”

“…The medullary epithelial molecule responsible for adhesion to doublepositive thymocytes does not seem, a priori, to correspond to any previously described adhesion molecule [12-141: indeed, complex formation is more efficient at 4°C than at 37 "C, and is Ca2+/Mg2+ independent. Furthermore, the putative adhesion molecule on the E-5 plasma membrane is a trypsin-sensitive glycoprotein, the glycosylated moiety of which is not involved in adhesion to thymocytes [15]. In the present work, we report the identification, isolation, partial characterization and binding specificity of this novel adhesion molecule found both on E-5 cells and on thymic medullary epithelial cells in sku.…”