Study On The Correlation Between Regulatory T Cells And Dendritic Cells In The Pathogenesis Of Mycosis Fungoides

IntroductionMycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma (CTCL), named from the mushroom-like figure of the skin lesion. The characteristic morphology of MF is the epidermotropical proliferation of small to intermediate-sized atypical lymphocytes with hyperchromatic, cerebriform nuclei surrounded by clear cytoplasm. Classical MF was divided into three clinical stages:patches, plaques and tumors. Most of the patients have been persistent in patch-stage for many years or even decades. A minority of the patients will progress into plaques and tumors. The underlying mechanisms which cause these differences have not been well understood. Previous studies showed that regulatory T cells (Treg) and dendritic cells (DC) played a vital role in these processes. But the extent of impact and the relationship between these two facts have not been reported. The purpose of this study is to find out the distribution of Treg and DC in each stage of MF and the relationship between them.Part I The distribution of Treg and DC in each stage of MFPurpose To find out the distribution of Treg and DC in each stage of MF, and the relationship between the characteristics of distribution and tumor stage.Methods Utilize immunohistochemical staining to detect the distributive characters of Treg and three types of dendritic cells:LC, dDC and pDC in each stage of MF, normal skin as control. Labeling Treg with FOXP3, LC with CD207, dDC with CD209, and pDC with CD303.Results FOXP3 express on the nuclei of Treg. The number of tumor infiltrated Treg is remarkable higher in patch/plaque stage than in tumor stage. There are no Treg in normal skin. In contrast to normal skin, there is a mild increase of LC in upper dermis in each stage of MF. CD207 express on the membrane and within the cytoplasm of LC in a dot-like pattern. The number of dDC increases along with the progression of MF in a stage-dependent pattern. CD209 locate in the membrane of dDC. The number of pDC increases mildly in each stage of MF equally. CD303 locate in the membrane of pDC.Conclusions The number of tumor infiltrated Treg is correlated with MF stage. It is remarkably higher in patch/plaque stage than that in tumor stage. There is mild increasing of LC and pDC in each stage of MF. But we only observed close correlation between the proliferation of dDC and stage, with the highest in tumor stage.Part II The spatial as well as temporal relationship between Treg and dDC in MFPurpose Disclose the spatial and temporal relationship between Treg and dDC in each stage of MF.Methods Calculate the average number of FOXP3 and CD209 immuno-staining positive cells per HPF. Utilize Triple immunofluorescence staining to find out the spatial relationship between Treg and dDC.Results The average number of Treg and dDC in patches, plaques and tumors is 36,41,10 and 9,21,49, respectively. Treg infiltrate into amid of tumor T cells, while dDC distribute predominantly at the peripheral area of tumor next to normal tissues, there is no close relationship between them.Conclusions The number of tumor infiltrated Treg in patch/plaque stage of MF is higher than in tumor stage. On the contrary, the number of dDC increases along with MF progression. The close spatial relationship between Treg and dDC has not been found in each stage of MF.