Infection-induced inflammatory reactions involve a strong increase in dendritic cells (DCs) at the infection site and draining lymph nodes (dLNs). Whether inflammatory DCs are recruited to these locations or differentiate locally, and what their functional relevance is, remain unclear. Here we showed that during Leishmania infection, monocytes were recruited to the dermis and differentiated into "dermal monocyte-derived DCs," which subsequently migrated into the dLNs. In addition, monocyte recruitment to the dLNs resulted in the differentiation into "LN monocyte-derived DCs." Analysis of the kinetics of monocyte differentiation into DCs, susceptibility to infection, IL-12 production, and L. major-specific T cell stimulation potential suggest that dermal monocyte-derived DCs controlled the induction of protective T helper 1 responses against Leishmania. Thus, the demonstration of monocyte differentiation potential into DCs during in vivo infection and of local DC differentiation in inflammatory foci suggests that de novo formed monocyte-derived DCs are essential in T cell immunity against pathogens.

No abstract

SUMMARY Interleukin 2 (IL-2) promotes Foxp3+-regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we demonstrated that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1–dependent mechanism. However, once the immune response resolved, some Treg cells down-regulated CD25, up-regulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones. Thus, unlike its effects on conventional Treg cells, IL-2 inhibits TFR cell responses.

The question of which dendritic cells (DCs) respond to pulmonary antigens and cross-prime CD8+ T cells remains controversial. We show that influenza-specific CD8+ T cell priming is controlled by different DCs at different times after infection. Whereas early priming is controlled by both CD103+CD11blo and CD103-CD11bhi DCs, CD103-CD11bhi DCs dominate antigen presentation at the peak of infection. Moreover, CD103-CD11bhi DCs capture exogenous antigens in the lung and directly cross-prime CD8+ T cells in the draining lymph node without transferring antigen to CD8α+ DCs. Finally, we show that CD103-CD11bhi DCs are the only DCs to express CD70 after influenza infection and that CD70 expression on CD103-CD11bhi DCs licenses them to expand CD8+ T cells responding to both influenza and exogenous ovalbumin.

Although cognate encounters between CCR7-expressing antigen-bearing dendritic cells (DCs) and CCR7+ naïve T cells take place within the T cell zone of lymph nodes, it is unknown whether co-localization of the DCs and T cells within the T cell area is obligate for effector generation. Here, we show that, following nematode infection, antigen-bearing DCs and CD4+ T cells upregulate CXCR5 and co-localize in a CXCL13, B cell and lymphotoxin-dependent fashion outside of the T zone. Importantly, lymphotoxin-expressing B cells, CXCL13 and CXCR5-expressing DCs and T cells are also necessary for development of interleukin 4 (IL-4) producing TH2 cells, suggesting that TH2 differentiation can initiate outside of the T cell zone.