Genetic Control of Immunity to Plasmodium yoelii Sporozoites.

摘要

Using a rodent malaria system, we have shown that protective immunity to the preerythrocytic stages of malaria is genetically controlled by Major Histocompatibility Complex and non-Major Histocompatibility Complex genes. Ten congenic strains of mice were immunized with irradiated sporozoites of Plasmodium yoelii. When challenged with viable sporozoites, only two strains had a high proportion of animals that did not develop blood stage infections. Immunity did not correlate with antisporozoite antibody levels. Two protective mechanisms exist determined by non-H-2 genes, and each mechanisms is further controlled by H-2 linked Immune response genes. On the BALB background only H-2d mice are protected, and protection is abolished by depleting CD8+ T cells. In contrast, on the B10 background only H-2q mice are strongly protected, and protection is not affected by CD8+ T cells depletion. If similar complex genetic regulation of immunity occurs in the human malarias, it will be a major hurdle for vaccine development. Keywords: Plasmodium yoelii; H-2 linked Ir genes; Sporozoites; T-cell immunity; Rodent malaria; Non-H2 genes; CD8+ Effector cells; H-2 Genes; Genetic control of immunity; Histocompatibility; Microbiology; Immunology; Reprints. (JG)