Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding the immunological response of the T cells. Immuno-proteasome activity is impaired following irradiation. 7- Immunosuppression and cancer. Malignant cells develop molecular mechanisms, e.g., HLA-G expression, to escape immune recognition. Higher cancer incidence in organ recipients may be attributable to their immunosuppressive treatment and to IR. 8- Autoimmune reactions. Ionizing radiation can break self-tolerance as observed in individuals exposed in Hiroshima and Nagasaki and in children with thyroid disease after Chernobyl accident. 9- Perturbation of immunological homeostasis. Both experimental and epidemiological data have demonstrated that IR disturbs T-cell homeostasis. Conclusion. The effects of IR on the immune system which combine immunosuppression and immuno-modulation, may be responsible for inadequate responses of the body to foreign aggressions allowing for the development of infections or cancers. More attention should be given to the immune system in the context of exposures to IR. (authors)