Glucocorticoids stimulate the division of rat pancreatic islet tumour cells in tissue culture.

The effects of hormones on the growth of beta cells, obtained from an X-ray induced transplantable rat islet cell tumour, were studied in tissue culture. Cells were cultured in Dulbecco's modified medium containing 1% bovine serum albumin, which did not permit fibroblast outgrowth. Among a variety of different hormones tested, the most potent growth promoters were found to be the corticosteroids whose potency was related to their glucocorticoid activity. After 5 weeks in culture with prednisolone (270 nmol/l), all cells stained immunohistochemically for insulin, although the insulin content was decreased to 10% that of fresh cells. Growth hormone (10 micrograms/ml) stimulated DNA replication to a small extent in the presence or absence of glucocorticoids. Insulin secretion from freshly prepared tumour cells was not stimulated by glucose but was increased two- to threefold by leucine (20 mmol/l) plus theophylline (5 mmol/l). This pattern of stimulation was observed still in cells cultured for 4 weeks in prednisolone-supplemented medium.

Transplantation of the pancreas in man.

This short communication reports on the outcome of eleven insulin dependent diabetics with microangiopathy of the retinae and kidneys treated with vascularised segmental pancreatic and renal allografts from the same donor. Cyclosporin A was the sole immunosuppressant.

Stimulation of lymphocyte proliferation by non-lymphoid porcine tissue cells.

Cultured porcine non-lymphoid cells, characterized by biochemical and morphological criteria, were derived from different tissues of individuals typed by serological and mixed lymphocyte culture methods for gene products of the major histocompatibility complex. These cultured cells have been used as stimulators in mixed lymphocyte-tissue cell cultures in order to investigate (1) the magnitude, kinetics and dose-dependence of lymphocyte transformation caused by tissue cells compared with that caused by lymphocytes as stimulators; (2) the relationship between the expression of serologically detected Ia-like antigens by tissue cells and their ability to cause lymphocyte transformation; (3) the genetic control of stimulation by tissue cells and by lymphocytes and (4) the expression and genetic control of lymphocyte stimulatory properties restricted to tissue cells and absent from lymphocytes. It has been shown that some but not all kinds of tissue cells can stimulate allogeneic lymphocytes strongly and that the characteristics of such stimulation are similar to those observed in mixed lymphocyte cultures. Strong stimulation by tissue cells does not always correlate with the expression of serologically detectable Ia-like antigens, but appears to be controlled by the major histocompatibility complex. There is evidence that certain tissue cells possess lymphocyte stimulatory properties not shared by lymphocytes. Preliminary data suggest that such tissue cell specific stimulation is not controlled by the major histocompatibility complex, though more detailed genetic analysis is required.

Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells.

The in vitro action of the immunosuppressive agent Cyclospirin A has been investigated using porcine cells. Lymphocyte proliferation induced in response to transplantation antigens and phytohaemagglutinin (PHA), was inhibited by this agent at doses that failed to inhibit mitogenisis in response to sheep anti-pig IgM, growth of kidney cell monolayers, and leukocyte migration.

Modification of lymphocyte responsiveness in vitro by lambda carrageenan compared with colloidal silica and depletion of surface adherent cells.

The effects of the immunosuppressive sulphated polygalactan lambda carrageenan on in vitro models of allograft immunity were compared with the effects of removing macrophages (surface adherent and/or phagocytic cells) by established methods. Carrageenan depressed the primary mixed lymphocyte reactions, but not to the same extent as the removal of macrophages. 2-Mercaptoethanol restored the response. Secondary mixed lymphocyte reactions and responses to phytohaemaglutinin were depressed by carrageenan but not by the removal of macrophages, and in these systems 2-mercaptoethanol failed to restore the responses of carrageenan-treated cultures. In contrast, cell-mediated cytolysis by presensitized lymphocytes was not affected by carrageenan or by colloidal silica. Carrageenan depressed cell-mediated cytolysis only if it was present during the sensitization of the effector cells. We conclude that carrageenan can have two dose-related effects in vitro: one on the macrophage and one on the responding lymphocyte.