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CD8 T Cells from a Novel T Cell Receptor Transgenic Mouse Induce Liver-Stage Immunity That Can Be Boosted by Blood-Stage Infection in Rodent Malaria
Malaria is a disease caused by Plasmodium species, which have a highly complex life cycle involving both liver and blood stages of mammalian infection. To prevent disease, one strategy has been to induce CD8+ T cells against liver-stage parasites, usually by immunization with stage-specific antigens. Here we describe a T cell receptor specificity that recognizes an antigen expressed in both the liver and blood stages of several rodent Plasmodium species. We generated a T cell receptor transgenic mouse with this specificity and showed that T cells from this line could protect against liver-stage infection. We used this novel tool to identify the site and cell-type involved in priming to a recently developed intravenous attenuated sporozoite vaccine shown to have efficacy in humans. We showed that CD8+ T cells with this specificity could protect against liver-stage infection while causing pathology to the blood stage. Finally, we provided evidence that T cells with cross-stage specificity can be primed and boosted on alternative stages, raising the possibility that antigens expressed in multiple stages might be ideal vaccine candidates for generating strong immunity to liver-stage parasites.
Vyšlo v časopise: CD8 T Cells from a Novel T Cell Receptor Transgenic Mouse Induce Liver-Stage Immunity That Can Be Boosted by Blood-Stage Infection in Rodent Malaria. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004135
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004135Souhrn
Malaria is a disease caused by Plasmodium species, which have a highly complex life cycle involving both liver and blood stages of mammalian infection. To prevent disease, one strategy has been to induce CD8+ T cells against liver-stage parasites, usually by immunization with stage-specific antigens. Here we describe a T cell receptor specificity that recognizes an antigen expressed in both the liver and blood stages of several rodent Plasmodium species. We generated a T cell receptor transgenic mouse with this specificity and showed that T cells from this line could protect against liver-stage infection. We used this novel tool to identify the site and cell-type involved in priming to a recently developed intravenous attenuated sporozoite vaccine shown to have efficacy in humans. We showed that CD8+ T cells with this specificity could protect against liver-stage infection while causing pathology to the blood stage. Finally, we provided evidence that T cells with cross-stage specificity can be primed and boosted on alternative stages, raising the possibility that antigens expressed in multiple stages might be ideal vaccine candidates for generating strong immunity to liver-stage parasites.
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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Combined Systems Approaches Reveal Highly Plastic Responses to Antimicrobial Peptide Challenge inČlánek Two Novel Human Cytomegalovirus NK Cell Evasion Functions Target MICA for Lysosomal Degradation
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