Fernando Luis Da Cruz Fernandes, Mota; (1998) The immune microenvironment in HPV-related cervical neoplasia. Doctoral thesis (Ph.D), University College London.

Preview

Text The_immune_microenvironment_in.pdf Download (10MB) | Preview

Abstract

There is a strong body of evidence implicating human papillomaviruses (HPVs) as aetiological agents in the pathogenesis of cervical cancer and its precursor lesions, i.e. cervical intraepithelial neoplasia (CIN). Host cell-mediated immunosurveillance mechanisms may be of critical importance in the control of HPV-related cervical disease. The main objective of this thesis was to contribute to the understanding of these mechanisms involved in the local immunomodulation of HPV infected and/or transformed cervical epithelium. We have shown that the addition of mussel glycogen during the extraction of DNA for HPV 16 PCR increases the DNA yield and the detection of this oncogenic HPV type. With respect to antigen processing, the aspartic proteinase cathepsin E, which has been reported to play a role in presentation by class II MHC molecules is associated with cellular dedifferentiation in CIN lesions. HLA-DR antigens were expressed constitutively on the majority of Langerhans cells. In contrast, few Langerhans cells express HLA-DQ in normal cervix, but there was a steady upregulation of the proportion expressing HLA-DQ, which paralleled the severity of premalignant disease. In contrast to the epithelium, stromal CD1a+ cells expressed adhesion molecules. CD58 (LFA-3) was expressed constitutively by cervical keratinocytes, but not CD50 (ICAM-3) and CD86 (B7-2). Keratinocyte expression of TNF-a protein was downregulated, and EL-10 protein was detected in some CIN lesions. In high-grade disease there was an overall increase in the number of mucosal infiltrating immune cells, predominantly positive for CD11a (LFA-1). Finally, we have shown different patterns of CD3-induced T cell proliferative responses in the presence of supernatants from cultures of HPV-infected and/or transformed cervical epithelia, but no significant correlations were found between T cell proliferation and the concentrations of IL-l, IL-10, IL-12 and TNF-α in the culture media. Our results are consistent with a local response to CIN progression characterized by Langerhans cell activation and emigration, alterations in keratinocyte cell surface and cytokine production, and infiltration of immune cells.

Download activity - last month

Export as XMLJSONCSV

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item