Desensitization: II. Passive transfer of the desensitized state by serum from desensitized animals

Abstract

The present study was undertaken in an effort to elucidate the mechanism(s) responsible for desensitization, making use of both cutaneous and peritoneal manifestations of delayed hypersensitivity as parallel assay systems in the guinea pig model. Particular emphasis was placed on investigating the possibility of passively transferring desensitization with serum factors and attempting to characterize these. Our data support the hypothesis of an inhibitory environment in the anergic animal: The desensitized state was successfully transferred to immune recipients by the systemic administration of desensitized serum as measured by both skin testing and macrophage disappearance reaction (MDR). Transfer of the desensitized state is not due to residual antigen in donor sera and is nonspecific. Partial characterization of the serum inhibitor indicated that it is nondialyzable, heatstable at 56 °C for 30 min, but destroyed by heating at 80 °C for 60 min. Sephadex G-100 chromatography located the inhibitory activity in the size range of 10,000–45,000 daltons. Larger molecular weight fractions were devoid of inhibitory activity, suggesting that antibodies or immune complexes are not responsible for the effect observed and the inhibitory serum component is not associated with macroglobulins. The physicochemical properties of the desensitizing factor, and our previous finding that intravenous injection of lymphokines leads to transient cutaneous anergy, suggest that the desensitizing substances may represent endogenous lymphokines in the general circulation.