TY - JOUR
T1 - Protective CD8+ T cells against Plasmodium liver stages
T2 - Immunobiology of an 'unnatural' immune response
AU - Overstreet, Michael Glen
AU - Cockburn, Ian Andrew
AU - Chen, Yun Chi
AU - Zavala, Fidel
PY - 2008/10
Y1 - 2008/10
N2 - Immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by CD8+ T cells. In contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. In this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective CD8+ T cells. Upon biting, the malaria-infected mosquitoes deposit parasites in the skin, many of which eventually exit to the bloodstream and infect hepatocytes. However, certain antigens, including the circumsporozoite (CS) protein, remain in the skin and are presented in the draining lymph node. These antigens prime specific CD8+ T cells, which migrate to the liver where they eliminate parasitized hepatocytes. We discuss the relevance of the different tissue compartments involved in the induction and effector phases of this response, as well as the cellular requirements for priming and memory development of CD8+ T cells, which include a complete dependence on dendritic cells and a near absolute need for CD4+ T-cell help. Finally, we discuss the impact of the immunodominant CS protein on this protection and the implications of these findings for vaccine design.
AB - Immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by CD8+ T cells. In contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. In this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective CD8+ T cells. Upon biting, the malaria-infected mosquitoes deposit parasites in the skin, many of which eventually exit to the bloodstream and infect hepatocytes. However, certain antigens, including the circumsporozoite (CS) protein, remain in the skin and are presented in the draining lymph node. These antigens prime specific CD8+ T cells, which migrate to the liver where they eliminate parasitized hepatocytes. We discuss the relevance of the different tissue compartments involved in the induction and effector phases of this response, as well as the cellular requirements for priming and memory development of CD8+ T cells, which include a complete dependence on dendritic cells and a near absolute need for CD4+ T-cell help. Finally, we discuss the impact of the immunodominant CS protein on this protection and the implications of these findings for vaccine design.
KW - CD8 T cells
KW - Liver
KW - Lymph node
KW - Malaria
KW - Memory
KW - Sporozoite
UR - http://www.scopus.com/inward/record.url?scp=52049105157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52049105157&partnerID=8YFLogxK
U2 - 10.1111/j.1600-065X.2008.00671.x
DO - 10.1111/j.1600-065X.2008.00671.x
M3 - Review article
C2 - 18837788
AN - SCOPUS:52049105157
SN - 0105-2896
VL - 225
SP - 272
EP - 283
JO - Immunological reviews
JF - Immunological reviews
IS - 1
ER -