Background: Skin Lesions of cutaneous lupus erythematosus (LE) have a number of infiltrating T cells, and these T cells and their related cytokines are involved in the development of skin lesions. Objective: In order to verify the rotes of T cells and their related cytokines, we compared the cytokine profiles of LE-like skin lesions in experimentally-induced knock out (KO) mice and autoimmune-prone mice. Methods: Lesional skin samples were obtained from CD4 KO mice and TCR alpha KO mice of the B6 background treated with ultraviolet B light (UVBL) and fluorouracil (FU), and MRL/lpr mice. The levels of mRNAs for TNF-alpha, IFN-gamma, IL-2, IL-4, IL-10 and IL-12 were determined by RT-PCR in these skin samples. Results: Combination treatment with UVBL and FU to TCR alpha KO mice and CD4 KO mice revealed the importance of CD4(+) CD8(-) gamma delta T cells in the induction of drug induced cutaneous LE. Moreover, IL-12, IFN-gamma and TNF-alpha were upregutated in TCR alpha KO mice treated with UVBL and FU. In contrast, IFN-gamma was not elevated in the spontaneous LE-like skin lesions of MRL/lpr mice. Conclusions: Cytokine profile pattern varies from strain to strain, and that murine cutaneous LE models, like human LE patients, manifest a wide range of immunological abnormalities, including cytokines. (c) 2005 Japanese Society for Investigative Dermatology. Elsevier Ireland Ltd. All rights reserved.