Amyloid-inducing factor and immunological unresponsiveness.

Several groups of investigators have shown that the induction time for experimental murine amyloidosis may be accelerated by passive transfer ofviable spleen cells or subcellular fractions of spleen cells from casein-treated donors to isogeneicrecipients (Werdelin and Ranl0v, 1966; Hultgren, Druet, and Janigan, 1967; Dreher and Letterer, 1970). On rare occasions the recipient mice appear to have developed amyloidosis without further treatment (Ranl0v, 1967; Willerson, Gordon, Talal, and Barth, 1969), but in the majority of studies they have been subjected to additional manipulations including sublethal total body x-irradiation, administration of nitrogen mustard, orrepeatedinjectionsofantigenic substances such as casein. For these and other reasons the mode ofmurine amyloid transfer has remained obscure and there has been virtually no agreement as to the nature of the cells or factors which are responsible for the accelerated induction of amyloid or even as to whether the pathogenesis of amyloid in the recipient animals is based on recognizable immunological principles. Indeed, Clerici, Mocarelli, De Ferrari, and Villa (1969) concluded that transfer amyloidosis was unlikely to be caused by adoptive immunity, since x-irradiated C57 inbred mice failed to develop amyloid after receiving intraperitoneal or intravenous injections of 5 to 30 million thoracic duct cells from isogenic amyloidotic donor animals, and Willerson and others (1969) produced evidence to suggest that an amyloid inducer or soluble amyloid rather than a specific functioning subcellular organelle was responsible for the transfer success in their experiments with Swiss white andC3H mice strains. In the following paper we wish to report a series of experiments in which spleen and peritoneal cells were interchanged between casein-treated and non-caseintreated outbred guinea-pigs. In these experiments, guinea-pigs receiving intraperitoneal injections of spleen cells from donors rendered tolerant to casein developed amyloid at an accelerated rate. This finding suggests the presence of a subcellular factor which is capable of crossing histocompatibility barriers and which may be a mediator of high-dosage immune paralysis as well as amyloidosis.