Enhanced expression of H-2K and H-2D antigens on reticulocytes infected with Plasmodium yoelii

The 17XNL strain of Plasmodium yoelii induces a highly effective and permanent T-cell dependent immunity in mice of the CBA strain; the lethal variant P. yoelii 17XL and P. berghei (ANKA) fail to activate an effective immune response in the same host. These differences in immunogenicity are unexplained. We recently observed that in CBA/CaJ mice the intracellular blood stages of P. yoelii 17XNL were almost exclusively within reticulocytes whereas lethal P. yoelii 17XL and P. berghei (ANKA), at comparable stages of infection, were predominantly erythrocytic. Induction of a reticulocytosis converted the normally lethal P. yoelii 17XL infection into a nonlethal one, and reticulocytic P. yoelii was shown to be more immunogenic than the erythrocytic form. Since one of the differences between reticulocytes and erythrocytes that might have influenced the development of immunity was greater expression of MHC antigens of the former cell type we examined the expression of H-2K, H-2D and Ia on reticulocytes infected with P. yoelii 17XNL. These cells showed a very marked increase in H-2K and D antigen expression compared to normal reticulocytes or erythrocytes. No Ia was detected. Red blood cells (RBC) infected with lethal P. yoelii 17XL or P. berghei showed no increase in H-2K or H-2D antigen expression. Finally, the level of expression of H-2K on P. yoelii 17XNL parasitized red blood cells from different strains of mice correlated closely with the ability of these strains to control the infection.     

Thioridazine and EKG anomalies

Summary Acute i.v. infusion but not daily oral administration of thioridazine-HCl in the dog produced EKG anomalies similar to those reported in psychiatric patients taking this drug. Lack of EKG effects after thioridazine-5-sulfoxide infusion and presence of anomalies after thioridazine at equivalent doses suggests further evaluation of the relationship between reported plasma levels of thioridazine and its ring-sulfoxide in association with EKG changes.This study was supported, in part, by a Grant-in-Aid from Boehringer-Ingelheim, Ltd. Sandoz, Inc. kindly provided thioridazine HCl (Mellaril^®) and thioridazine-5-sulfoxide.