Interactions between naive T cells and DCs are believed to contro

Interactions between naive T cells and DCs are believed to control both primary T cell activation and subsequent T cell fate, and thus the outcome of the adaptive immune response. How DCs perform such a complex feat remains unclear. The currently Roxadustat solubility dmso accepted view is that immune outcomes are determined primarily by factors external to both DCs and T cells, such as the microbe-derived signals that radically alter the activation state of DCs [1]. An alternative view is that the DC lineage is comprised of distinct DC subpopulations committed to predetermined functions [2, 3]. These functions, including generation of T cell tolerance or immunity,

are then amplified by exposure to microbial signals. In this model, the outcome GS-1101 in vitro of an immune response depends upon how T cells integrate signals derived from the mix of preprogrammed DCs to which they are exposed during priming. The DC lineage in the mouse has been subdivided into populations on the basis of surface phenotypes that correlate with differences in ontogeny, microanatomical location and requirements for specific cytokines and transcription factors. In the currently

accepted schema, expression of high levels of CD11c and MHC II defines conventional DCs (cDCs), which are generated from precursors residing Benzatropine in secondary lymphoid organs such as LN and spleen [1]. cDCs are then subdivided into CD8+ (Xcr1+Clec9a+) and CD11b+ (Sirpa+) subsets that correlate with the human CD141+ (Xcr1+Clec9a+) and CD1c+ (Sirpa+) DC subsets (reviewed in [4, 5]). In addition to cDCs, LNs contain migratory DCs (mDCs) that have entered the LN via afferent lymphatic vessels.

In murine LNs draining the skin, mDCs are defined as CD11cintMHC IIhigh, and comprise four distinct subsets: radioresistant migratory epidermal Langerhans cells (mLCs) and three subsets of radiosensitive migratory dermal DCs (mDDCs) that differ in expression of CD11b and CD207/Langerin [6] and/or CD103 (reviewed in [1, 7]). Migration of antigen-bearing DCs into the LN is essential for generating both peripheral adaptive immune responses and tolerance to antigens present within non-lymphoid tissues such as the skin [6, 8]. Migratory DC subset equivalents in humans have not been established fully, but recent reports have identified multiple distinct DC populations in human skin and LNs [9-11]. Attributing specific functions to individual DC subsets has proven far more difficult than the analysis of phenotype. DC subsets capable of driving CD4 and CD8 responses, regulating T helper type 1 (Th1)/Th2/Th17 bias, generating inducible regulatory T cells (Tregs) and/or inducing tolerance are highly model-dependent (see Table 1).

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