title: The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.
abstract: Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity among residents of malaria endemic areas indicate that memory responses to Plasmodium Ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. In contrast, multiple exposures to radiation-attenuated Plasmodium berghei sporozoites (Pb γ-spz) induce long-lasting protective immunity to experimental sporozoite challenge. We previously demonstrated that sterile protection induced by Pb γ-spz is MHC class I-dependent and CD8 T cells are the key effectors. IFN-γ(+) CD8 T cells that arise in Pb γ-spz-immunized B6 mice are found predominantly in the liver and are sensitive to levels of liver-stage Ag depot and they express CD44(hi)CD62L(lo) markers indicative of effector/effector memory phenotype. The developmentally related central memory CD8 T (TCM) cells express elevated levels of CD122 (IL-15Rβ), which suggests that CD8 TCM cells depend on IL-15 for maintenance. Using IL-15-deficient mice, we demonstrate in this study that although protective immunity is inducible in these mice, protection is short-lived, mainly owing to the inability of CD8 TCM cells to survive in the IL-15-deficient milieu. We present a hypothesis consistent with a model whereby intrahepatic CD8 TCM cells, being maintained by IL-15-mediated survival and basal proliferation, are conscripted into the CD8 effector/effector memory T cell pool during subsequent infections.
authors.affiliation: Department of Cellular Immunology, Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Stasya
authors.initials: S
authors.lastname: Zarling
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Berenzon
authors.forename: Sarat
authors.initials: S
authors.lastname: Dalai
authors.forename: Dmitry
authors.initials: D
authors.lastname: Liepinsh
authors.forename: Nick
authors.initials: N
authors.lastname: Steers
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000276:immunology* / Q000528:radiation effects; D034101:Sporozoites / Q000276:immunology
chemical_list: D019409:Interleukin-15; D017780:Malaria Vaccines; D007371:Interferon-gamma