CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin epithelial cells (ECs) and its T-cell–expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by ECs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of ECs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, whereas after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation was associated with the production of chemokines and the attraction of lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of ECs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the EC's response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and the EC's capacity to attract PBMCs. The fact that HPV attenuates CD40 signaling in ECs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia.