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Systemic suppression of contact hypersensitivity associated with suppressor lymphocytes: is a lesion in DNA an
1Basic Research Program-Litton Bionetics Inc., NCI Frederick Cancer Research Facility, Maryland.
Abstract:
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.
Insights
DNA alterations initiated by radiation may trigger suppressor lymphocytes, leading to suppressed contact hypersensitivity (CHS). This immune suppression is transferable via cells when DNA is damaged, but not when DNA is unaffected.
Area of Science:
- Immunology
- Photobiology
- Molecular Biology
Background:
- Systemic suppression of contact hypersensitivity (CHS) in mice is induced by UVB and methoxsalen/UVA radiation.
- These radiation types cause DNA damage, suggesting a role for molecular alterations in CHS suppression.
Purpose of the Study:
- To investigate the role of DNA alterations in radiation-induced CHS suppression.
- To determine if DNA interaction is essential for the development of suppressor lymphocyte-mediated CHS suppression.
Main Methods:
- Mice were exposed to various radiation modalities (UVB, UVA, X-ray, visible light) with or without photosensitizers (methoxsalen, 5-methylisopsoralen, rose bengal, eosin).
- DNA interaction and CHS suppression were assessed.
- The transferability of CHS suppression via lymphoid cells was tested.
Main Results:
- UVB, methoxsalen/UVA, X-ray, and 5-methylisopsoralen/UVA induced transferable CHS suppression, correlating with DNA damage.
- Rose bengal/visible light caused non-transferable CHS suppression without DNA lesions.
- Eosin/visible light did not induce CHS suppression.
Conclusions:
- Molecular alterations in DNA appear to be an initiating or essential step in suppressor lymphocyte-mediated CHS suppression.
- The mechanism of CHS suppression differs when DNA interaction is absent.