Acute upregulation of an NKG2D ligand promotes rapid reorganization of a local immune compartment with pleiotropic effects on carcinogenesis

Nature Immunology 9: 146-154, 2008

Speaker: 謝政原                                                   Time:13:10~14:00, May 14, 2008

Commentator: 黎煥耀 老師                                Place: Room 601

Abstract:

It has been shown that the major histocompatibility complex (MHC) class Ib proteins Rae-1(mouse) and MICA (human) are up-regulated in carcinomas and inflammatory lesion. These proteins engage with the activating receptor NKG2D, which is expressed by lymphocytes, such as NKT cells and gd T cells. Whether NKG2D ligands might initiate immunosurveillance and/or inflammation by acting as primary activators of an immune compartment has been raised but remained unresolved. To evaluate the intrinsic capacity of acute Rae-1 upregulation to regulate the immune responses in a tissue, the authors designed a tetracycline inducible system-based transgenic mouse in which Rae-1 expression is induced specifically in the epidermis by doxycycline. Seventy-two hours after doxycycline treatment, they detected rounded skin-specific Vg5Vd1 TCRgd⁺intraepithelial T cells and Langerhans cells, and the changed organization of these immune cells followed by infiltrating unconventional αβ T cells which are NKG2D⁺NK1.1⁺CD4^–CD8^– and contain specific TCRβ variable regions. They further found that the Tcrg^-V5^–/^–Tcrd^-V1^–/^–mice were more susceptibility to tumors induced by a two-stage carcinogenesis regimen suggesting that  the skin-specific T cells have tumor-supressing function. Conversely, the Langerhans cell–deficient mice showed more resistance to tumor formation implying that some unknown mechanism may contribute to the Langerhan cell–mediated tumor promotion. These results provide new insight into the early phases of tumor immunosurveillance in tissue and reveal that the multifaceted immunosurveillance response may be raised by acutely up-regulated NKG2D ligands.

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