Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals

Surojit Sarkar, Yevgeniy Yuzefpolskiy, Hanxi Xiao, Florian M. Baumann, Soojin Yim, David J. Lee, Dominik Schenten, Vandana Kalia

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Abstract

IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88-IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1-MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections. The Journ Al of Immunology, 2018, 201: 3641-3650.

Original languageEnglish (US)
Pages (from-to)3641-3650
Number of pages10
JournalJournal of Immunology
Volume201
Issue number12
DOIs
Publication statusPublished - Dec 15 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sarkar, S., Yuzefpolskiy, Y., Xiao, H., Baumann, F. M., Yim, S., Lee, D. J., ... Kalia, V. (2018). Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals. Journal of Immunology, 201(12), 3641-3650. https://doi.org/10.4049/jimmunol.1800906