Cellular and molecular induction of skin homing receptors on T cells

The recruitment of immune cells is crucial for immune defenses during skin infection. T cells use a specific combination of receptors and adhesion molecules to adhere to the vascular endothelium before infiltrating the skin. The expression of skin homing receptors is induced upon T cell activation by dendritic cells (DCs). Furthermore, factors present in the lymphoid environment during activation can affect receptor expression patterns on T cells. Commonly, there are only few DCs present in peripheral blood and it is a difficult process to isolate them. It has therefore become acceptable method to activate T cells through the T cell receptor with monoclonal antibodies binding to CD3 and CD28. The aim of this project was to study how the expression of CLA, CCR4, CCR10, alpha1 integrin and alpha4 integrin on T cells was induced, since they are all involved in T cell homing to the skin. The main focus was on the development of cell culture models that capture dendritic cell interactions with T cells and the subsequent expression of skin homing receptors on T cells. Furthermore, the effects of the antimicrobial peptide LL-37 and vitamin D on T cell proliferation and the skin homing molecule expression were studied. The results show that stimulation with CD3/CD28 antibodies and DCs has different effects on the expression of skin homing receptors on T cells, specially of CCR4 and CLA. Expression of homing molecules (CLA, CCR4 and alpha 4 integrin) on T cells was associated with increased maturation of DCs. Our observation that DCs stimulate only subset of T cells indicates that they may be a better choice and more representative for in vivo conditions. LL-37 and vitamin D differently affected the skin homing molecule expression on T cells and T cell proliferation is affected by LL-37. It is concluded that T cell activation should be carefully evaluated because the degree of activation and receptor expression depends on the choice of method applied.