Focus Session 2: Prediction of allergy

Allergic contact dermatitis (ACD) results from an unbalanced and exaggerated T-cell response against low molecular, highly reactive chemicals penetrating the skin. Both CD4 and CD8 T lymphocytes are involved in the expression of ACD, with CD8 lymphocytes being the major effector cells. The role of CD4 lymphocytes is more complex, with T helper (Th) 1 cells that co-operate with CD8 cells in disease expression and IL-10-producing CD4 cells which down-regulate hapten-specific immune responses. The eczematous reaction ensues mainly from T-cell release of pro-inflammatory cytokines and cytotoxic activity. In situ activated Th1 and T cytotoxic (Tc) 1 lymphocytes secrete IFN-g, TNF-a and IL-17, which induce MHC class II and ICAM-1 expression on keratinocytes and promote their secretion of chemokines, such as MCP-1, IP-10, RANTES, and I-309. These chemokines direct the accumulation of selective T-cell subsets and are fundamental for the amplification of the inflammatory reaction. T-cells infiltrating ACD reactions express FAS ligand and perforin, and are cytotoxic for haptenloaded keratinocytes in vitro. Cytotoxic capacity differs among the several T-cell subsets involved in ACD, with CD8 lymphocytes that can target both resting and activated keratinocytes, and Th1 cells that can kill only IFN-g pre-activated keratinocytes. Modulation of skin immune responses is critical to avoid excessive tissue damage. Although severalmechanismscan be involvedin the terminationof the inflammatory reaction, a relevant role is likely played by IL-10 secreting CD4 lymphocytes. These cells suppress hapten-specific CD4 and CD8 T-cell responses by blocking the maturation and antigen presenting functions of dendritic cells. Distinct T-cell subsets display a different pattern of chemokine receptor, and are thus differently recruited in the skin during ACD.