Modification of immune response by low dose ionizing radiation: role of apoptosis

Acute as well as fractionated whole body exposures to low doses (<50 cGy) of ionizing radiation (LDR) have been reported to alter several immunological parameters in experimental animals. It is, however, not clear whether the augmentation of immune response by LDR will be observed for all responses and across genetic barriers. Since several proteins including p53 are synthesized following radiation exposure, the role of p53 and consequently that of activation induced apoptosis in the immunomodulation by LDR also remained to be evaluated. Experiments were, therefore, carried out in two different strains of inbred mice viz. C57BL/6 and BALB/c, exposed to fractionated LDR (4 cGy/day, 5 days/week, total dose 20 cGy) and subsequently stimulated with the polyclonal mitogen Con A or immunized with Mycobacterium vaccae or dinitrofluorobenzene (DNFB) for delayed type hypersensitivity (DTH) response. The proliferation of spleen cells in response to con A as measured by [3H]thymidine incorporation was significantly higher in 20 cGy-irradiated C57BL/6 mice as compared with that in the Con A-stimulated cells from sham-irradiated controls. The same response was suppressed by LDR in BALB/c mice. On the other hand, DTH to M. vaccae as well as DNFB was suppressed in C57BL/6 mice while DTH to M. vaccae was augmented in BALB/c mice and that to DNFB was not significantly affected following same dose. The augmentation of response to con A in C57BL/6 mice was prominent in CD4− (CD8+) T cells and was marked by the decrease in the proportion of cells expressing p53 as estimated by flow cytometry. Reduction in expression of p53 was accompanied by reduced apoptosis, as measured by TUNEL® assay, in the Con A-stimulated spleen cells of irradiated C57BL/6 mice when compared with that in the sham-treated controls. The spleen cells of BALB/c mice showed exactly opposite profiles in this respect. Thus alteration in the immune response following LDR depends on antigen, type of response as well as the strain of mice used. Furthermore, the alterations in the expression of pro-apoptosis gene p53 and activation induced apoptosis in the effector or regulatory cells seem to contribute to the end result.