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

2007; Oxford University Press; Volume: 196; Issue: 12 Linguagem: Inglês

10.1086/522965

1537-6613

Julius Clemence R. Hafalla, Urvashi Rai, Dabeiba Bernal‐Rubio, Ana Rodrı́guez, Fidel Zavala,

Immunotherapy and Immune Responses

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.