Mature T cells arise from progenitor cells by a complex and poorly understood process of differentiation in the thymus. Thymocytes can be divided into four major compartments on the basis of surface expression of the murine equivalents of CD8 (Lyt-2) and CD4 (L3T4) (refs 1,2). Functionally mature thymocytes express only CD4 or CD8. The CD4-8- subset contains progenitor cells capable of giving rise to all the phenotypic and functional classes of T cells on adoptive transfer. The function of the major population, the CD4+8+ cells, which carry both the CD4 and CD8 antigens, in thymic differentiation is controversial. It has been variously proposed that they represent terminally differentiated cells which die in the thymus or that they represent an intermediate stage and can differentiate into functionally and phenotypically mature single positive T cells. The CD3-antigen receptor complex is probably important in thymic differentiation. The receptor has two functions: recognition and transmembrane signalling. To help clarify the function of CD4+8+ thymocytes in thymic differentiation, the expression and function of the antigen receptor complex on these cells should be determined. We show here that most CD4+8+ thymocytes express CD3 which functions in transmembrane signalling. The consequences of this signalling differ from those in mature T cells, however, in that the CD4+8+ cells do not secrete IL-2, express IL-2 receptor, or proliferate.

To study the origin of and the degree of T-cell antigen receptor (TCR) diversity of Thy-1+ dendritic epidermal cells (Thy-1+ dECs) in mice, we have developed a monoclonal antibody (mAb 536) to the yb TCR. mAb 536 binds to and stimulates interleukin 2 secretion from Thy-1+ dEC but not cells that express TCR composed of a and 13 chains. mAb 536 precipitates CD3-associated y and 6 chains from lysates of radioiodinated Thy-1+ dECs. Analysis of a panel of hybridomas that express y6 TCR indicated that mAb 536 defines an epitope of the variable region (Vy3) gene product. Flow cytometric analysis revealed that expression of Vy3 in the adult mouse is restricted to cells in the epidermis, where essentially all Thy-1+ cells are Vy3'. The majority of CD3' cells in the 14-day fetal thymus also express Vy3. These results indicate that the T-cell complement in epidermis are cells that express y6 TCR and that the diversity of antigens recognized by the cells might be restricted by the use of a single V,, gene segment. Finally, the data raise the intriguing possibility that Thy-1+ dECs may arise from precursors that are among the first to emerge from the developing thymus. This suggests that V gene usage during thymocyte development is highly regulated and has important consequences on the tissue localization and function of the emerging cells. As in other developing tissues, it appears that programmed and transient gene expression determines the fate of the emerging cells.Two types of CD3-associated heterodimeric proteins encoded by rearranging antigen receptor genes are found on T cells in lymphoid organs. The vast majority of T cells express receptors composed of clonally distributed ap heterodimers (1). These T cells generally express the accessory molecules CD4 or CD8 and are capable of specific recognition of antigen in the context of products of the major histocompatibility complex. The second type of T cells express heterodimers composed of the products of the y (2-5) and 8 (6-10) loci and generally do not express CD4 or CD8. The function of this second type of T cell has not been established, although it has recently been suggested that they are capable of recognition of the major histocompatibility complex (11,12).It has recently been shown that Thy-1+ dendritic cells present in the skin of mice (dECs) express CD3-associated heterodimers encoded by the T-cell antigen receptor (TCR) y and 8 genes (7,(13)(14)(15)(16). Thy-1+ dECs are capable of functions associated with conventional af3 T cells, including direct cytotoxic destruction of cells when targeted via lectins or anti-CD3 antibodies and interleukin 2 (IL-2) secretion upon activation (17). These facts raise the possibility that these cells might be capable of antigen-specific recognition and provide an important component of the immunological armamentarium in the skin. It is therefore of considerable interest to determine the origin of and to assess the degree of potential TCR diversity in these cells. In this report, we describe the production of a monocl...

Calcium release, measured as luminescence of the protein aequorin, was measured simultaneously with membrane potential and isometric tension in single muscle fibers of the barnacle (Balanus nubilus). Deuterium oxide inhibited calcium release and isometric tension but did not affect membrane potential, a result consistent with the postulate that deuterium oxide inhibits the coupling between excitation and contraction.

No abstract