Immunosuppression in murine renal cell carcinoma. II. Identification of responsible lymphoid cell phenotypes and examination of elimination of suppression

Abstract

In our companion paper we have reported that cell-mediated immunity of mice bearing renal cell carcinoma is profoundly suppressed. The non-responsiveness of such animals was found to be attributable to Renca cells themselves and to splenic lymphoid cells that down-regulate other fully capable lymphoid cells. In this communication the lymphoid cell source of suppression within Renca-bearing mice has been explored with the aim of identifying phenotypes of the responsible cells, the manner by which suppression is mediated, and initial ways by which suppression may be eliminated. A plastic-adherent cell bearing the Thy1.2 surface marker as well as the Lyt1 and Lyt2 antigens has been found to operate, perhaps in conjunction with macrophages, to down-regulate lymphokine-activated killer (LAK) cell development for natural killer (NK) and non-NK targets that include Renca cells themselves. The splenic suppressor cells lost the capacity to suppress the NK response of normal recipient mice upon shallow irradiation (250 rad) prior to adoptive transfer. Spleen cells, presumably macrophages, from Renca-bearing mice were found to suppress the generation of LAK and NK cells in vitro by synthesizing prostaglandins. Indomethacin, a prostaglandin synthetase inhibitor, blocked the induction of suppression both in vitro and in vivo, suggesting the presence of endogenous prostaglandins in Renca-bearing mice. The suppression seen in Renca-bearing mice that derives from multiple sources and has been prevented by two separate methods has been discussed from the viewpoint of the inter-relatedness of the sources.