Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.621931
Keywords
interleukin-1; dendritic cells; CD4(+) T cells; CD8(+) T cells; cellular adjuvant; vaccination; cancer immunotherapy
Categories
Funding
- FWO-SB
- FWO [G045318]
- UGent Methusalem [CYRE 340941]
- Advanced ERC grant [CYRE 340941]
- Orionis Biosciences BV
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The three-signal paradigm aims to capture how the innate immune system instructs adaptive immune responses through three defined actions, with a focus on the activities of IL-1 in shaping the adaptive immune response in DCs and T cells.
The three-signal paradigm tries to capture how the innate immune system instructs adaptive immune responses in three well-defined actions: (1) presentation of antigenic peptides in the context of MHC molecules, which allows for a specific T cell response; (2) T cell co-stimulation, which breaks T cell tolerance; and (3) secretion of polarizing cytokines in the priming environment, thereby specializing T cell immunity. The three-signal model provides an empirical framework for innate instruction of adaptive immunity, but mainly discusses STAT-dependent cytokines in T cell activation and differentiation, while the multi-faceted roles of type I IFNs and IL-1 cytokine superfamily members are often neglected. IL-1 alpha and IL-1 beta are pro-inflammatory cytokines, produced following damage to the host (release of DAMPs) or upon innate recognition of PAMPs. IL-1 activity on both DCs and T cells can further shape the adaptive immune response with variable outcomes. IL-1 signaling in DCs promotes their ability to induce T cell activation, but also direct action of IL-1 on both CD4(+) and CD8(+) T cells, either alone or in synergy with prototypical polarizing cytokines, influences T cell differentiation under different conditions. The activities of IL-1 form a direct bridge between innate and adaptive immunity and could therefore be clinically translatable in the context of prophylactic and therapeutic strategies to empower the formation of T cell immunity. Understanding the modalities of IL-1 activity during T cell activation thus could hold major implications for rational development of the next generation of vaccine adjuvants.
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