Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: is a lesion in DNA an essential step in the pathway?

Exposure of mice to ultraviolet B (UVB) radiation and treatment with methoxsalen and UVA radiation produces a systemic suppression of contact hypersensitivity (CHS) that is associated with suppressor lymphocytes. Both UVB and methoxsalen and UVA radiation produce lesions in DNA, and this suggests that alterations in that molecule might be an essential step in the pathway. This possibility has been explored by testing the effect of other modalities that do and do not interact with DNA. Treatment of mice with superficial X radiation, which mainly produces single-strand breaks in DNA, or with 5-methylisopsoralen and UVA radiation, which produces monofunctional adducts in DNA, results in systemic suppression of CHS. In both instances, the suppression can be transferred to untreated mice by injection of lymphoid cells obtained from suppressed mice. Treatment of mice with rose bengal and visible (greater than 400 nm) radiation, a photochemical interaction that does not produce lesions in DNA, results in systemic suppression of CHS; however, in contrast to the other treatments, the suppression cannot be transferred with lymphoid cells. In addition, treatment of mice with eosin and visible radiation, which also does not interact with DNA, did not produce suppression of CHS. These findings suggest that a molecular alteration in DNA may be either an initiating or an essential step in the development of the systemic suppression of CHS that is mediated by suppressor lymphocytes.