Efficient development of plasmodium liver stage-specific memory CD8+ T cells during the course of blood-stage malarial infection |
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Authors: | Hafalla Julius C R Rai Urvashi Bernal-Rubio Dabeiba Rodriguez Ana Zavala Fidel |
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Institution: | Department of Medical Parasitology, New York University School of Medicine, 341 E. 25th Street, New York, NY 10010, USA. |
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Abstract: | 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. |
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