Efficient Development of Plasmodium Liver Stage-Specific Memory CD8⁺ T Cells during the Course of Blood-Stage Malarial Infection

• Published in: The Journal of infectious diseases Vol. 196; no. 12; pp. 1827 - 1835
• Main Authors: Hafalla, Julius C. R., Rai, Urvashi, Bernal-Rubio, Dabeiba, Rodriguez, Ana, Zavala, Fidel
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 15-12-2007
• Subjects: Animals; Anopheles - parasitology; Bacterial diseases; Bacterial sepsis; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Epitopes, T-Lymphocyte - immunology; Female; Human bacterial diseases; Human protozoal diseases; Immunity; Immunization; Immunologic Memory - immunology; Infections; Infectious diseases; Liver; Liver - parasitology; Malaria; Malaria - blood; Malaria - immunology; Malaria - parasitology; Malaria Vaccines - immunology; Medical sciences; Memory; Mice; Mice, Inbred BALB C; Parasites; Parasitic diseases; Plasmodium yoelii - growth & development; Plasmodium yoelii - immunology; Plasmodium yoelii - radiation effects; Protozoal diseases; Sporozoites; Sporozoites - growth & development; Sporozoites - immunology; Sporozoites - radiation effects; T lymphocytes; Transgenic animals; Vaccinia virus - genetics; Vaccinia virus - immunology; Protozoa; Apicomplexa; Protozoal disease; Malaria; Digestive system; Liver; Parasitosis; Bacteremia; Infection; Plasmodium; Blood cell; T-Lymphocyte; Bacteriosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/522965

Immunity to Plasmodium liver stages in individuals in malaria-endemic areas is inextricably linked to concomitant blood-stage parasitemia. Although Plasmodium sporozoite infection induces measurable CD8⁺ T cell responses, the development of memory T cells during active erythrocytic infection remains uncharacterized. Using transgenic T cells, we assessed antigen-specific effector CD8⁺ T cell responses induced by normal (NorSpz) and radiation-attenuated (IrrSpz) Plasmodium yoelii sporozoites. The magnitude, phenotypic activation, and differentiation pathway of CD8⁺ T cells were similarly induced by NorSpz and IrrSpz. Moreover, in normal mice, memory T cells elicited after priming with NorSpz and IrrSpz generated identical recall responses after a heterologous boost strategy. Furthermore, these recall responses exhibited comparable in vivo antiparasite activity. Our results indicate that sporozoites that retain their infective capacity induce memory CD8⁺ T cells that are robustly recalled by secondary immunization. Thus, erythrocytic infection does not preclude the establishment of memory CD8⁺ T cell responses to malarial liver stages.