Interleukin-1 as Innate Mediator of T Cell Immunity

• Published in: Frontiers in immunology 2021-01, Vol.11, p.621931
• Main Authors: Van Den Eeckhout, Bram, Tavernier, Jan, Gerlo, Sarah
• Format: Article
• Language: English
• Subjects: Antigen Presentation; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; cellular adjuvant; dendritic cells; Dendritic Cells - immunology; Humans; Immunology; interleukin-1; Interleukin-1alpha - immunology; Interleukin-1beta - immunology; Lymphocyte Activation; vaccination
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.621931

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-1α and IL-1β 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.