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Review
. 2003 Jul 21;198(2):185-90.
doi: 10.1084/jem.20030737. Epub 2003 Jul 14.

The importance of CD11b+ dendritic cells in CD4+ T cell activation in vivo: with help from interleukin 1

Akiko Iwasaki  1
Affiliations
Review

The importance of CD11b+ dendritic cells in CD4+ T cell activation in vivo: with help from interleukin 1

Akiko Iwasaki. J Exp Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
A proposed mechanism of CD4+ T cell priming after Leishmania major infection. Infectious metacyclic promastigotes are introduced into the dermis of the host by the bite of a sandfly or through needle inoculation. The promastigotes are taken up by skin dermal macrophages, within which the parasite can replicate in the form of amastigotes. Amastigotes released from ruptured macrophages can infect nearby dermal DCs, which results in the activation of dermal DCs and release of factors such as IL-1 and IL-12. In the case of needle injection of a large number of promastigotes (105–107), the promastigotes can be taken up by the dermal DCs and processed for MHC class II presentation. Either the amastigote-infected dermal DCs (following sandfly bite) or promastigote-loaded dermal DCs (after needle injection of >105 parasite) migrate to the draining LNs and enter the T cell area to present parasite antigens to CD4+ T cells in the context of MHC class II (reference 5). Langerhans cells infected with the parasite may also migrate to the draining LNs but whether they present parasite antigens and induce CD4+ T cell activation needs to be further elucidated. IL-1 secreted from the DCs promotes Th1 differentiation of the antigen-specific T cells in several mutually nonexclusive ways: (a) IL-1 may facilitate the migration of dermal DCs from the site of infection to the draining LNs (reference 44), (b) IL-1 may induce activation of DCs through signaling of their IL-1RI/IL-1RAcP complex via the MyD88 pathway, and (c) IL-1 may directly activate CD4+ T cells leading to their Th1 differentiation. Signaling of IL-1RI on DCs may lead to increase in the expression levels of costimulatory molecules and release of cytokines such as IL-12 and IL-18. Alternatively, a separate microbial stimulus present on Leishmania parasite may trigger the secretion of IL-12, which is enhanced by the concomitant IL-1 signaling. In the resistant strains, this IL-1 production from DCs is optimal, leading to the activation of CD4+ T cells to secrete IFN-γ (references and 6). In contrast, IL-1 secretion from DCs is reduced in the susceptible strains, leading to suboptimal DC activation and Th2 differentiation (references and 6). Factors other than IL-1 likely also contribute to the intrinsic differences between the CD11b+ DCs of the susceptible and the resistant strains, such as differences in the expression of costimulatory molecules (reference 5), other cytokines, chemokine/chemokine receptors, and perhaps TLRs.
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References

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