Distinct T cell subsets and cytokine production in cultures derived from transformation zone and squamous intraepithelial lesion biopsies of the uterine cervix.

in American Journal of Reproductive Immunology (2003), 49(1), 6-13

PROBLEM: The characterization of lymphocytes issued from squamous intraepithelial lesions (SIL) and from the transformation zone (TZ), where the majority of SIL occur, is important to understand the role ... [more ▼]

PROBLEM: The characterization of lymphocytes issued from squamous intraepithelial lesions (SIL) and from the transformation zone (TZ), where the majority of SIL occur, is important to understand the role of immunity in SIL development. METHOD OF STUDY: We compared lymphocyte populations of the TZ and SIL with those of normal exocervix, using a technique allowing for the isolation of lymphocytes, either from the epithelium or from the underlying stroma of small biopsies. RESULTS: The majority of cells derived from the epithelium of all biopsies were CD8+ T cells. Some SIL-derived cultures were characterized by an increased proportion of activated TCRgammadelta+. The production of the immunosuppressive cytokine IL10 was significantly higher in lymphocyte cultures from the normal TZ in comparison with the exocervix. A decreased percentage of effector T cells was observed in cultures derived from the stroma of normal TZ (TCRgammadelta+) or SIL (CD8+) in comparison with the exocervix. CONCLUSIONS: Our results suggest that a low proportion of effector T cells and IL10 production could contribute to the predisposition of the TZ to the development of SIL and to the progression of SIL to cervical cancer. [less ▲]

Dendritic cells induce the death of human papillomavirus-transformed keratinocytes

in FASEB Journal (2001), 15(13), 2521-2523

IL10 production in cultures of lymphocytes derived from biopsies of normal exocervix, transformation zone and squamous intraepithelial lesion

in Monsonego, J. (Ed.) 4th International Multidisciplinary Congress - Eurogin 2000 (2000)

The immune system appears to play a role in the development of squamous intraepithelial lesions (SIL) and their progression to cancer. We have developed a technique to isolate and cultivate lymphocytes ... [more ▼]

The immune system appears to play a role in the development of squamous intraepithelial lesions (SIL) and their progression to cancer. We have developed a technique to isolate and cultivate lymphocytes either from the epithelium or from the underlying stroma of small biopsies from the normal exocervix, the transformation zone (TZ) and SIL. The majority of cells derived from the epithelium of all biopsies were CD8+ T cells. No major difference was observed for the lymphocyte phenotype. Among all cytokines tested by ELISA (IL10, IL4 and IFNγ), only IL10 was significantly higher in the TZ in comparison with the exocervix. In cultures derived from the stroma, a decreased percentage in T cells was observed in the TZ and SIL in comparison with the exocervix. This decrease in T cells concerned CD8+ (SIL) and TCRγδ+ T cells (TZ and SIL). We did not observe any difference in IL10 or IL4 production, although patients with SIL produced more IFNγ. The higher levels of IL10 production by lymphocytes derived from the epithelium of the TZ might contribute to the predisposition of this region to cervical carcinogenesis. [less ▲]

Generation of T lymphocytes from the epithelium and stroma of squamous pre-neoplastic lesions of the uterine cervix.

in Journal of Immunological Methods (1999), 223(1), 123-9

In this study, we have developed a simple and efficient technique for the isolation of viable lymphocytes from the epithelium and stroma of small pre-neoplastic squamous intraepithelial lesions (SIL) of ... [more ▼]

In this study, we have developed a simple and efficient technique for the isolation of viable lymphocytes from the epithelium and stroma of small pre-neoplastic squamous intraepithelial lesions (SIL) of the uterine cervix. Following the separation of the epithelium from the stroma using dispase II, both biopsy fragments were used to generate T lymphocytes. The stroma-derived lymphocytes were obtained by collecting and culturing the cells migrating out of the biopsy in the presence of IL2 (50 U/ml). An average of 0.7 x 10(6) and 1.4 x 10(6) lymphocytes could be obtained after 20 and 30 days of culture, respectively. For the expansion of lymphocytes derived from the pre-neoplastic epithelium (SIL) it was necessary to use a combination of irradiated peripheral blood mononuclear cells (PBMC) as a feeder layer with PHA (0.1%), in addition to IL2 (50 U/ml). Interestingly, these lymphocytes could be obtained using either allogeneic or syngeneic PBMCs. With this protocol, we were able to generate up to 100 x 10(6) lymphocytes from the epithelium, the majority of which were T lymphocytes. [less ▲]