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- PMID: 24101691
- UKPMCID: 24101691
- DOI: 10.1128/IAI.01091-13
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IL-27R signalling regulates memory CD4+ T cell populations and suppresses rapid inflammatory responses during secondary malaria infection.
Findlay, Emily Gwyer; Villegas-Mendez, Ana; O'Regan, Noelle; de Souza, J Brian; Grady, Lisa-Marie; Saris, Christiaan J; Riley, Eleanor M; Couper, Kevin N
Infection and immunity. 2013;.
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Full-text held externally
- PMID: 24101691
- UKPMCID: 24101691
- DOI: 10.1128/IAI.01091-13
Abstract
IL-27 is known to control primary CD4(+) T cell responses during a variety of different infections but its role in regulating memory CD4(+) T responses has not been investigated in any model. In this study we have examined the functional importance of IL-27R signalling in regulating the formation and maintenance of memory CD4(+) T cells following malaria infection and in controlling their subsequent reactivation during secondary parasite challenge. We demonstrate that although the primary effector/memory CD4(+) T cell response was greater in IL-27R deficient (WSX-1(-/-)) mice following P. berghei NK65 infection compared with WT mice, there were no significant differences in the size of the maintained memory CD4(+) T population(s) at 20 weeks post-infection in the spleen, liver or bone marrow of WSX-1(-/-) mice compared with WT mice. However, the composition of the memory CD4(+) T cell pool was slightly altered in WSX-1(-/-) mice following clearance of primary malaria infection, with elevated numbers of late effector memory CD4(+) T cells in the spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX-1(-/-) mice displayed significantly enhanced parasite control compared with WT mice following re-challenge with homologous malaria parasites. Improved parasite control in WSX-1(-/-) mice during secondary infection was associated with elevated systemic production of multiple inflammatory innate and adaptive cytokines and extremely rapid proliferation of antigen-experienced T cells in the liver. These data are the first to demonstrate that IL-27R signalling plays a role in regulating the magnitude and quality of secondary immune responses during re-challenge infections.