After immunizing mice with type I, but not type II, adjuvants and pathogens, Leal and Huang et al. observed reorganization of lymph node (LN)-resident cDCs from the periphery to the T cell zone, dependent on CCR7, where they activate and expand antigen-specific T cells. Simultaneously, inflammatory monocytes (MO) producing IL-12 accumulated in the T cell zone from the blood through high endothelial venules, which was dependent on CCR2 and distributed heterogeneously, possibly due to non-uniform lymphatic drainage of agonists. Effector differentiation (Tbet+TCF1-) of activated T cells correlated with MO proximity and was impaired when MO infiltration or IL-12 production was blocked.
Contributed by Alex Najibi
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.
Author Info: (1) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (2) Department of Immunology, Cent
Author Info: (1) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (2) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (3) Department of Surgery, University of Washington School of Medicine, Seattle, WA 98109, USA. (4) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (5) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (6) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (7) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. (8) Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98109, USA. gernermy@uw.edu.
