The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

The activation of HPV-specific T cells within the cervical microenvironment is likely to play an important part in the natural history of cervical int raepithelial neoplasia (CIN). The extent and the type of T cell activation will depend critically on the expression of MHC, costimulatory cell surface molecules and cytokines by keratinocytes and Langerhans cells within the c ervical lesion. Expression of MHC class II (HLA-DR and -DQ), costimulatory/ adhesion molecules (CD11a/18, CD50, CD54, CD58 and CD86) and cytokines (tum our necrosis factor-alpha (TNF-alpha) and IL-10) was therefore investigated by immunohistochemistry in normal squamous epithelium (n = 12), low-grade (n = 23) and high-grade (n = 18) squamous intraepithelial lesions of the ce rvix. CIN progression was associated with de novo expression of HLA-DR and CD54, and increased expression of CD58 by keratinocytes. However, significa ntly, there was no expression of any adhesion/costimulation molecule by epi thelial Langerhans cells in any cervical biopsy studied. Furthermore, TNF-a lpha, a potent activator of Langerhans cells, was expressed constitutively by basal keratinocytes in normal cervix (12+/12), but expression of this cy tokine was absent in a number of CIN samples (20+/23 for low-grade, 12+/18 for high-grade CIN). Conversely, the suppressive cytokine IL-10 was absent in normal epithelium (0+/12), but was upregulated in a number of CIN lesion s (12+/23 for low-grade, 8+/18 for high-grade CIN). The restricted expressi on of costimulation/adhesion molecules and the nature of the cytokine micro environment within the epithelium may act to limit effective immune respons es in some CIN lesions.