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Immunologic memory is one of the cardinal features of adoptive immune responses and is inextricably linked to lasting
protection against infections. While many re-infections are prevented by memory T and B cells, malaria re-infections occur
frequently and the reasons for the absence of lasting protection in endemic areas remain poorly understood. By contrast,
exposures of humans and laboratory rodents to radiation-attenuated
sporozoites (γ-spz) induce sterile and
durable protection against experimental sporozoite challenge. The presence of memory CD4 T cells has been shown to
be associated with lasting protection in humans exposed P. falciparum (Pf)
-spz. Studies focusing on durable protection
induced in mice with P. yoelii and P. berghei
-spz have, instead, implicated memory CD8 T cells as crucial features of lasting
protection. We observed that in the Pb
-spz model, MHC class I-dependent liver-stage (LS) Ag-specific memory CD8 T cells
are indispensable for the maintenance of protection. We hypothesize that long-term protection to malaria, whether mediated
by CD8 or CD4 T cells, can be induced and maintained. As such, it requires the formation and persistence of memory T cells
with a reservoir of central memory cells maintained in part by LSAg-depot, IL-15 and possibly IL-4 and other cytokines that
promote conscription of IFN-γ producing effector/effector memory CD8 T cells during re-infections.
Urszula Krzych received her PhD degree from Rutgers University and subsequently as a Postdoctoral fellow studied with the late Eli Sercarz at UCLA. She currently
heads the Department of Cellular Immunology at WRAIR, where she has been conducting research on the various aspects of malaria, most notably investigating
immune mechanisms of protection induced by malaria vaccines in humans and mice. She is also affiliated with the George Washington University, Washington, DC.
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