CD40 is required for protective immunity against liver stage Plasmodium infection

• Published in: The Journal of immunology (1950) 2015-03, Vol.194 (5), p.2268-2279
• Main Authors: Murray, Sara A, Mohar, Isaac, Miller, Jessica L, Brempelis, Katherine J, Vaughan, Ashley M, Kappe, Stefan H I, Crispe, Ian N
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD40 Antigens - deficiency; CD40 Antigens - genetics; CD40 Antigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - parasitology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - transplantation; Dendritic Cells - immunology; Dendritic Cells - parasitology; Dendritic Cells - pathology; Female; Gene Deletion; Gene Expression; Hepatocytes - immunology; Hepatocytes - parasitology; Hepatocytes - pathology; Immunity, Innate; Liver - immunology; Liver - parasitology; Liver - pathology; Lymphocyte Activation; Malaria - immunology; Malaria - parasitology; Malaria - pathology; Malaria - prevention & control; Malaria Vaccines - administration & dosage; Mice; Mice, Inbred C57BL; Plasmodium yoelii; Plasmodium yoelii - immunology; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Signal Transduction; Sporozoites - chemistry; Sporozoites - immunology; Vaccines, Attenuated
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401724

The costimulatory molecule CD40 enhances immunity through several distinct roles in T cell activation and T cell interaction with other immune cells. In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite. Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves. Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice. Thus, protective immunity generated during immunization with fabb/f(-) was largely dependent on effective APC licensing via CD40 signaling.