Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix.

Abstract Objectives. Humoral and cellular immune responses are likely to play a key role for the clearance or persistence and progression of high risk (HR) HPV-associated cervical lesions. Although there are many studies describing the systemic T-cell responses to HPV16 and 18 proteins, few data are available regarding the cellular mucosal immune responses. We used immunohistochemistry to characterize populations of T-immune cells (CD4+, CD8+, CD45RO+) in HR-HPV-infected precancerous and cancerous lesions of the uterine cervix. Methods. Four biopsies from normal cervix, 9 CIN1 which have regressed (rCIN), 5 CIN1 which have progressed (pCIN) to high grade lesions, 13 CIN3 and 11 invasive carcinomas were included. All dysplasias and carcinomas were HR-HPV-positive and low-risk-HPV-negative. They were stained with monoclonal antibodies specific for CD4, CD8 and CD45RO and examined by microscopy. Statistical analysis. The Kruskal–Wallis test and the Siegel's and Castelan's method were used. Results. CD4+ cells predominated in regressing CIN1 both within the stroma and the epithelium with the highest CD4+/CD8+ ratio compared with pCIN1, CIN3 and invasive carcinoma. At the exception of CD45RO+ cells, T cells were detected with similar frequencies in both pCIN1 and CIN3. However, in 7 out of 10 CIN3, CD4+ and CD8+ cells were visible as organized lymphoid follicle structure. The CD8+ and CD45RO+ cells far exceeded the CD4+ cells in invasive cancers. Conclusions. Density and distribution of immune T cells depend on the malignant potential of HR-HPV lesions. These results suggest that the studied lymphocyte subsets have an important role to fulfil during the natural history of HR-HPV-associated lesions.