Editors' ChoiceIMMUNITY

Border Security in the Lung: Detail(s) at the Direction of CD1c+ Dendritic Cells

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Science Translational Medicine  17 Apr 2013:
Vol. 5, Issue 181, pp. 181ec67
DOI: 10.1126/scitranslmed.3006318

The generation of effective immune responses requires a diverse functional repertoire of T lymphocytes to be generated and distributed to relevant anatomic sites. Because many infectious diseases gain entry through epithelial surfaces, the maintenance of protective immunity at these mucosal surfaces is of paramount importance. The mechanisms by which individual T cells are programmed with distinct functional and homing properties remain poorly understood. This remains a limitation of vaccination strategies for many diseases, including influenza.

It is against this backdrop that Yu et al. provide insight into distinct activation patterns of CD8 T lymphocytes by subsets of dendritic cells (DCs). The authors first performed a series of experiments to compare and contrast the two major dendritic cell populations resident in human lung tissue. DCs from human surgical lung specimens and human DCs obtained from a humanized mouse model gave similar results. Both CD141+ and CD1c+ DCs expanded after inoculation with live attenuated influenza vaccine, and each DC subset could elicit similar proliferative and cytolytic capacity from cocultured CD8 T cells. However, only CD1c+ DCs stimulated the expression of CD103 on CD8 T lymphocytes. In a series of in vitro and in vivo experiments, the authors went on to establish that CD103 expression by CD8 T cells correlates with adherence to epithelial cells and that this function is CD103-dependent. Last, the authors demonstrated that transforming growth factor–β (TGF-β) regulates CD103 expression by CD8 cells in vitro and in vivo. Although both DC subsets are capable of expressing TGF-β and its receptors, CD1c+ DCs are capable of expressing genes required for activation of latent TGF-β.

These data suggest that despite considerable phenotypic and functional overlap, CD1c+, but not CD141+, DCs confer upon their target CD8 T cells the ability to adhere to epithelium, directing these cells to remain resident within mucosal tissue. Thus, vaccination strategies that optimize CD1c+ DC activation might lead to more effective mucosal immunity against common respiratory infections, including influenza. Additional insights into the intricate mechanisms of DC–T cell interactions that control the magnitude, diversity, and distribution of immune cells are needed to advance our understanding of other emerging diseases and their treatment.

C. I. Yu et al., Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector t cells via the cytokine TGF-β. Immunity, published online 4 April 2013 (10.1016/j.immuni.2013.03.004). [Abstract]

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