Journal
JOURNAL OF IMMUNOLOGY
Volume 171, Issue 4, Pages 2024-2034Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.4.2024
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- NIAID NIH HHS [AI 46438] Funding Source: Medline
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We previously demonstrated that protection induced by radiation-attenuated (gamma) Plasmodium berghei sporozoites is linked to MHC class I-restricted CD8(+) T cells specific for exoerythrocytic-stage Ags, and that activated intrahepatic memory CD8(+) T cells are associated with protracted protection. In this study, we further investigated intrahepatic memory CD8+ T cells to elucidate mechanisms required for their maintenance. Using phenotypic markers indicative of activation (CD44, CD45RB), migration (CD62L), and IFN-gamma production, we identified two subsets of intrahepatic memory CD8(+) T cells: the CD44(high) CD45RB(low)CD62L(low)CDI22(low) phenotype, representing the dominant effector memory set, and the CD44(high)CD45RB(high)CD62L(low/high)CD122(high) phenotype, representing the central memory set. Only the effector memory CD8(+) T cells responded swiftly to sporozoite challenge by producing sustained IFN-gamma; the central memory T cells responded with delay, and the IFN-gamma reactivity was short-lived. In addition, the subsets of liver memory CD8(+) T cells segregated according to the expression of CD122 (IL-15R) in that only the central memory CD8(+) T cells were CD122 high, whereas the effector memory CD8(+) T cells were CD122(low). Moreover, the effector memory CD8(+) T cells declined as protection waned in mice treated with primaquine, a drug that interferes with the formation of liver-stage Ags. We propose that protracted protection induced by P. berghei radiation-attenuated sporozoites depends in part on a network of interactive liver memory CD8(+) T cell subsets, each representing a different phase of activation or differentiation, and the balance of which is profoundly affected by the repository of liver-stage Ag and EL-15.
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