Abstract
The rat monoclonal antibody (mAb) 4F1, raised against mouse thymic stromal cells, recognizes cortical epithelium in tissue sections of mouse thymus; however, in flow cytometry, activated leucocytes (T cells, B cells, and macrophages) and transformed thymocytes are also positive for the 4F1-antigen (4F1-Ag). Western blotting, under both reducing and nonreducing conditions, demonstrates that the molecule to which 4F1 binds is expressed in four forms, 29, 32, 40, and 43 kD, all of which carry N-linked carbohydrate; and that the structure is identical on epithelium and lymphocytes. The 4F1-Ag on cortical epithelium is partially sensitive to PI-PLC treatment, whereas on transformed epithelial and lymphoid cell lines, it was resistant to this enzyme. The molecule, therefore, may exist in both transmembrane and phosphoinositol-linked forms. In functional blocking experiments, mAb 4F1 gave inhibition of both T-cell proliferation in MLR and of cytotoxic T-cell killing of alloantigenic targets; it also blocked adhesion of transformed thymocytes to thymic epithelial cells in vitro. These molecular and functional characteristics suggest that the 4F1-Ag is a novel adhesion molecule that may be involved both in intrathymic T lymphocyte differentiation and in peripheral T-cell function.
Highlights
It is known that T lymphocyte differentiation takes place within the microenvironment of the thymus, the precise inductive and selective mechanisms whereby stromal cells of epithelial and haemopoietic origin are involved remain yet to be resolved (Marrack and Kappler, 1987; von Boehmer, 1988). specific signals that induce cellular differentiation in the thymus have not been identified, T-cell development requires close interaction between thymic microenvironmental cells and the developing lymphocytes (Stutman et al, 1969)
4F1, binds to all cortical epithelium and small patches of epithelial cells in the medulla of mouse thymus (Kanariou et al, 1989), and in the recent workshops on thymic epithelial antibodies has been defined as a CTES III reagent (Kampinga et al, 1989; Ladyman et al, 1991)
The molecule is expressed on the BW 5147 thymoma line and on epithelial thymoma cells grown in isolation from any lymphocytes (TM25.F1)
Summary
Specific signals that induce cellular differentiation in the thymus have not been identified, T-cell development requires close interaction between thymic microenvironmental cells (epithelium, dendritic cells, and macrophages) and the developing lymphocytes (Stutman et al, 1969) This interaction is likely to take two main forms: first, direct cell-cell contact involving cell-surface molecules, such as antigen receptors and MHC molecules, as well as accessory/adhesion molecules such as CD2, CD4, CD8, and LFA-3 (CD58); and second, interaction between soluble molecules, such as cytokines, and their cell-surface receptors (Bierer et al, 1989; Springer, 1990). A recent approach to the analysis of these intrathymic mechanisms has been to raise monoclonal antibodies (mAb) to molecules in/on thymic stromal cells (DeMaagd et al, 1985; Kanariou et al, 1989) These reagents, raised to both human and rodent thymus, have revealed considerable heterogeneity within the epithelial component of the mammalian thymic microenvironment. 4F1, binds to all cortical epithelium and small patches of epithelial cells in the medulla of mouse thymus (Kanariou et al, 1989), and in the recent workshops on thymic epithelial antibodies has been defined as a CTES (cluster of thymic epithelial staining) III reagent (Kampinga et al, 1989; Ladyman et al, 1991)
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