Abstract

Formaldehyde (FA) is a ubiquitous environmental pollutant and a group 1 carcinogen. CD8+ T cells are specific tumor killers in the adaptive immune system. In this study, 2.0 mg/m3 respiratory FA exposure to male mice was found to selectively reduce mature CD8+ T cells in the spleen and the CD8 T cells in the thymus. In order to monitor the exposure of FA in vitro, a fluorescent FA donor was utilized in the treatment of murine thymocytes. Cytotoxicity induced by FA was found to be not selective at single positive stage. Significant inhibition of the runt-related transcription factor-3, the critical transcriptional factors for CD8 lineage commitment, was found in FA-treated double positive cells. ThPOK, the transcriptional factor for CD4 commitment, was stimulated by FA in double positive cells. Increased expression of special AT-rich sequence-binding protein-1 and decreased expression of B-cell lymphoma/leukemia 11B, which are the upstream regulators of ThPOK and the runt-related transcription factor-3, were also observed in FA-treated double positive cells. These results demonstrate that FA could selectively inhibit the development of CD8+ T cells via the alteration of transcriptional factor expressions of thymocytes at double positive stages, which would potentially interfere with the immune defense against cancers.