Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

Abstract

The thymus plays a critical role in the generation of immunocompetent T lymphocytes. In the thymus, lymphocytes are in close contact with epithelial cells, and this contact is necessary for T-cell maturation. Using cultured human thymic epithelial (TE) cells, we have found that human thymocytes bind to human TE cells in vitro. Thymocytes bound to both allogeneic and autologous TE cells and to the epidermoid carcinoma cell line A431 but did not bind to epidermal keratinocytes or to thymic fibroblasts. Thymocyte binding to TE cells was trypsin-and cytochalasin B-sensitive. Indirect immunofluorescence assays showed that both mature (T6-, T3+) and immature (T6+, T3-) thymocytes bound TE cells. In our system, TE-thymocyte binding was not inhibited by antibodies to class I or class II major histocompatibility antigens. In vitro binding of thymocytes to TE cells may represent a correlate of in vivo TE-thymocyte interactions and provides a model system for the study of human intrathymic T-lymphocyte maturation and activation.Microscopists have long appreciated the extensive physical contact between the lymphoid and nonlymphoid elements of the thymus (1, 2). Direct contact of lymphoid and nonlymphoid elements within the thymus is necessary for generation of functionally mature, antigen-specific, major histocompatibility complex (MHC)-restricted T lymphocytes (3-6). Although the precise role played by the nonlymphoid component of the thymus is poorly understood, a number of interactions of developing thymocytes with nonlymphoid elements have been identified, including the formation of lymphoepithelial cell complexes in vivo, called thymic nurse cells (7), and the binding of thymocytes to macrophages and dendritic cells (8, 9). Farr et al. (10) recently observed a subpopulation of thymocytes within the thymic cortex expressing low levels of surface T-lymphocyte antigen receptors (Ti). Where these thymocytes were found in contact with epithelial cell processes, Ti molecules were localized in the region of thymocyte-epithelial contact. Recent development of methods for the long-term culture of human thymic-stromal elements (11), as well as development of monoclonal reagents specific for nonlymphoid components of human thymus (12-15), have made it possible to investigate thymocyte-stromal interactions in vitro. In this report we present evidence that human thymocytes bind to both autologous and allogeneic thymic epithelial (TE) tTo whom reprint requests should be addressed. 6588The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

The Reed-Sternberg cell/lymphocyte rosette. I. Properties of rosettes formed between Hodgkin's cell lines and allogeneic lymphocytes

“…Several leucocyte adherence molecules have been described in recent years: LFA antigens (CDI1/CD18) mediate leucocyte adherence responses (Pattarroyo et al, 1987;Suomalainen et al, 1986;Kishimoto et al, 1987); CD2 antigen expressed by thymocytes binds to its natural ligand LFA-3 expressed on thymic epithelial cells (Singer et al, 1987).…”

The human thymus

“…Contact between TE and thymocytes is mediated not only by MHC complex-TCR binding, but also by thymocyte CD2, LFA-1, and CD6 molecules binding to TE cell CD58 (LFA-3), CD54 (ICAM-1), and CD 165 (ALCAM) molecules, respectively (18)(19)(20)(21)(22)(23). Moreover, contact between TE cells and thymocytes has been shown to regulate TE cytokine production (24).…”

Morphological study of thymus stromal cells (TEL-2 cell) which play a role in the elimination of double positive immature thymocytes by phagocytosis

“…First, the immature DP thymocytes in the mouse in vitro undergo phenotypic alteration, follow the stages of rapid (within a few hours) development, and express a diversity of markers of CD4 CD8, and TCR ranging from CD810CD410TCR10 to (lD8hicD4hiTCiVF~'iOUS Stage (reviewed in Pawlowski and Staery, 1994;NikoliC-hgie, 1991). Second, the lymphocyte clusters grow in actual contact with the stroma1 cells (Singer et al, 1986;Witte et al, 1987).…”

“…Macrophages in vivo are thought to be a major component for the ingestion of apoptotic thymocytes (Duvall and Wyllie, 1986), whereas macrophages in vitro have been shown to play a significant role in the development of recognition and clearance of morphologically intact, though not apoptotic, immature double positive (DP) (CD4+/CD8 + ) thymocytes (Inaba et al, 1988). Some basic functional roles of the thymic epithelial cell are given as follows: 1) These cells can attach themselves to both mature and immature thymocytes (Jason and Janeway, 1984;Singer et al, 1986), and mediate selection of the T lymphocyte (Benoist and Mathias, 1989;Bill and Palmer, 1989). The lymphoepithelial cell complexes in murine thymuses are called thymic nurse cells .…”

“…The lymphoepithelial cell complexes in murine thymuses are called thymic nurse cells . These epithelial cells provide the necessary stimulus for the intrathymic differentiation of T-lymphocyte precursors via cell to cell contact, or the elaboration of a thymic hormone Singer et al, 1986). 2) The epithelial cells ingest syngeneic thymocytes in vitro (Jason and Janeway, 1984) and can be phagocytic, often containing internalized degenerated thymocytes, in both normal thymus (Singh, 1981) and pathological thymus tissue (Haelst, 1967;Mandel, 1968;Izard and de Harven, 1968;Bartel, 1979;Levine et al, 1981).…”