Research ArticleINNATE IMMUNITY

Innate cell microenvironments in lymph nodes shape the generation of T cell responses during type I inflammation

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Science Immunology  12 Feb 2021:
Vol. 6, Issue 56, eabb9435
DOI: 10.1126/sciimmunol.abb9435

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Teamwork for T cells

The location and interaction of innate immune cells in lymph nodes (LNs) contributes to the induction of T cell responses, yet the exact cells that contribute are unclear. Using advanced imaging techniques to characterize the spatial arrangement of innate and adaptive immune cells during TLR agonist-induced inflammation, Leal et al. show that LN-resident dendritic cells (DCs) and inflammatory monocytes cooperate to induce T cell responses. LN-resident DCs migrate to the T cell zone (TZ) in a CCR7-dependent manner and present antigen to T cells. Circulating monocytes enter the LN via high endothelial venules and become spatially polarized in the TZ, consequently inducing distinct inflammatory microenvironments and effector T cell subsets. Thus, DCs and monocytes in the LN TZ work together to induce T cell responses.

Abstract

Microanatomical organization of innate immune cells within lymph nodes (LNs) is critical for the generation of adaptive responses. In particular, steady-state LN-resident dendritic cells (Res cDCs) are strategically localized to intercept lymph-draining antigens. Whether myeloid cell organization changes during inflammation and how that might affect the generation of immune responses are unknown. Here, we report that during type I, but not type II, inflammation after adjuvant immunization or viral infection, antigen-presenting Res cDCs undergo CCR7-dependent intranodal repositioning from the LN periphery into the T cell zone (TZ) to elicit T cell priming. Concurrently, inflammatory monocytes infiltrate the LNs via local blood vessels, enter the TZ, and cooperate with Res cDCs by providing polarizing cytokines to optimize T cell effector differentiation. Monocyte infiltration is nonuniform across LNs, generating distinct microenvironments with varied local innate cell composition. These spatial microdomains are associated with divergent early T cell effector programming, indicating that innate microenvironments within LNs play a critical role in regulating the quality and heterogeneity of T cell responses. Together, our findings reveal that dynamic modulation of innate cell microenvironments during type I inflammation leads to optimized generation of adaptive immune responses to vaccines and infections.

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