Regulatory T cells play an important role in the prevention of murine melanocytic nevi and melanomas.

Melanocytic nevi are benign proliferations of pigment cells that can occasionally develop into melanomas. There is a significant correlation between increased nevus numbers and melanoma development. Our previous reports revealed that DMBA and TPA induced dysplastic nevi in C3H/HeN mice, with a potential to transform into melanomas. In order to understand the immune mechanisms behind this transformation, we applied increasing DMBA doses followed by TPA to the skin of C3H/HeN mice. We observed that increased doses of DMBA correlated well with increased numbers of nevi. The increased DMBA dose induced diminished immune responses and promoted the expansion of regulatory T cells that resulted in increased IL-10 and reduced IFNγ levels. Mice with increased nevus numbers had loss of p16 expression. These mice had increased migration of melanocytic cells to lymph nodes and a greater percent of lymph nodes produced immortalized melanocytic cell lines. DMBA-induced immunosuppression was lost in CD4KO mice. Lymphocytes in the CD4KO mice produced less IL-10 than CD8KO mice. Further, CD4KO mice had significantly reduced nevus numbers and size compared with wild type and CD8KO mice. These results suggest that regulatory T cells play a vital role in the incidence of nevi and their progression to melanoma.