Regulatory T Cells Play an important role in the prevention of Murine Melanocytic Nevi and Melanomas

Academic Article

Abstract

  • 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 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced dysplastic nevi in C3H/HeNmice, with a potential to transform intomelanomas. To understand the immune mechanisms behind this transformation, we applied increasing DMBA doses followed by TPAto the skin of C3H/HeNmice. Weobserved 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 (Treg) that resulted in increased IL10 and reduced IFN╬│ levels. Mice with increased nevus numbers had loss of p16 expression. These mice had increased migration of melanocytic cells to lymph nodes (LN) and a greater percent of LNs produced immortalized melanocytic cell lines. DMBA-induced immunosuppression was lost in CD4-knockout (KO) mice. Lymphocytes in the CD4KO mice produced less IL10 than CD8KO mice. Furthermore, CD4KO mice had significantly reduced nevus numbers and size comparedwithwild-type and CD8KO mice. These results suggest that Tregs play a vital role in the incidence of nevi and their progression to melanoma.
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    Author List

  • Nasti TH; Yusuf N; Sherwani MA; Athar M; Timares L; Elmets CA
  • Start Page

  • 165
  • End Page

  • 174
  • Volume

  • 14
  • Issue

  • 2