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


METHODS
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.
Monnier-Benoit
Sylvain
S
EA 3181, IFR 133, Université de Franche-Comté, Rue Ambroise Paré, 25000 Besançon, France.
Mauny
Frédéric
F
Riethmuller
Didier
D
Guerrini
Jean-Sébastien
JS
Căpîlna
Mihai
M
Félix
Sophie
S
Seillès
Estelle
E
Mougin
Christiane
C
Prétet
Jean-Luc
JL
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology / Q000821:virology*
D017493:Leukocyte Common Antigens