Antagonistic roles of CD4+ and CD8+ T-cells in 7,12-dimethylbenz(a)anthracene cutaneous carcinogenesis

Academic Article

Abstract

  • The role that cell-mediated immune responses play during cutaneous carcinogenesis has received little attention. In this study, we evaluated the contribution of CD4 and CD8 T cells in C3H/HeN mice that were subjected to a two-stage 7,12-dimethylbenz(a)anthracene (DMBA) initiation, 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion skin carcinogenesis protocol. In CD8 knockout (CD8 ) mice, allergic contact hypersensitivity to DMBA was reduced compared with wild-type (WT) C3H/HeN mice. On the other hand, CD4 knockout (CD4 ) mice developed an exaggerated contact hypersensitivity response. CD4 T cells from DMBA contact-sensitized mice preferentially produced interleukin 4 (IL-4), IL-10, and IL-17; CD8 T cells, on the other hand, secreted IFN-γ. When CD4 , CD8 , and WT mice were subjected to a standard two-stage DMBA/TPA cutaneous carcinogenesis protocol, the percentage of mice with tumors was much greater (P < 0.001) in CD8 mice than in WT mice. In contrast, the percentage of tumors was significantly less (P < 0.001) in CD4 mice than in WT mice. Similar results were obtained when the data were evaluated as the number of tumors per mouse. These findings indicate that (a) CD8 T cells are the predominant effector cells in allergic contact hypersensitivity to DMBA and that CD4 T cells have an inhibitory role and (b) the development of CD8 T cells plays a protective role in skin tumor development whereas CD4 T cells have the opposite effect. Manipulation of T-cell subpopulations that are induced by carcinogenic chemicals, like DMBA, could be a means of preventing skin cancers caused by these agents. ©2008 American Association for Cancer Research. + + -/- -/- + + -/- -/- -/- -/- + + + +
  • Published In

  • Cancer Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yusuf N; Nasti TH; Katiyar SK; Jacobs MK; Seibert MD; Ginsburg AC; Timares L; Xu H; Elmets CA
  • Start Page

  • 3924
  • End Page

  • 3930
  • Volume

  • 68
  • Issue

  • 10