Cytotoxic activity of invariant NKT cells in human allergic contact dermatitis

Cytotoxic activity of invariant NKT cells in human allergic contact dermatitis Background: The role of cytotoxicity of NKT-cells in the skin is not defined. There are two prototypic skin diseases in which epidermal Keratinocytes (KC) over-express CD1d, a MHC class-I-like molecule that present antigens to NKT-cells, in all layers of the epidermis and which there is infiltration of NKT-cells into the skin: allergic contact dermatitis (ACD) and psoriasis. In both diseases, NKT-cells are found within skin lesions, and within the epidermis in close apposition to CD1d bearing KC. This suggests that there may be direct KC-NKT-cell interactions that can affect the ongoing immune mediated inflammatory response. Purpose: To investigate the cytotoxic activity of invariant NKT cells in the skin and in human allergic contact dermatitis. Materials and methods: Paired skin biopsies from patch test reaction and normal skin were used for qPCR and immunohistochemistry. Calcein release assay was performed with NKT-cells as effector cells and KC as target cells. Results: Invariant NKT-cells are enriched in ACD reactions, but not in normal skin. Gene expression of cytotoxic effector molecules (perforin and granzymes) was higher in ACD lesions compared to normal skin (qPCR). Perforin and granzymes were found in invariant NKT-cells in patch test reactions, where as these molecules were also expressed by other cells, such as CD8+ conventional T-cells and NK-cells. Invariant gene expression of cytotoxic effector molecules is increased when these cells are activated in vitro by glycolipid and potent APC such as CD1d bearing monocytes, and KC in some cases as well. Cytotoxicity of NKT cells is increased versus keratinocytes. Conclusions: Human NKT-cells are in an activated state in ACD, and contribute to the tissue damage of allergic inflammation. These findings indicate that innate immunity plays an important role in the elicitation phase of ACD, and may represent a novel therapeutic target in allergic skin inflammation