"Out-of-field" effects of head-localized proton irradiation on peripheral immune parameters

The heads of Sprague-Dawley rats were irradiated with protons to total doses of 1.5, 3 and 4 Gy and euthanized 9-10 days later. Significant dose-dependent decreases were noted in thymus mass. Lymphocyte and platelet numbers were significantly reduced in blood. Flow cytometric analysis of blood and spleen showed that CD3+ T, CD3+/CD4+ TH, and CD3+/CD8+ TC cell numbers were low and proportions were significantly altered by radiation. CD4:CD8 ratios and CD45R+ B lymphocytes were unaffected. Spontaneous blastogenesis of blood and spleen leukocytes was significantly increased by radiation. Plasma TGF-beta 1 level in irradiated rats was consistently, but not significantly, higher than in non-irradiated animals. T and B cell proportions in lymph nodes from irradiated animals were similar to non-irradiated controls. Bone marrow from all irradiated groups had high CD90+/Gran+ cell numbers. The data show that head-localized proton irradiation at relatively modest doses can profoundly influence systemic distribution and composition of lymphocyte populations. The data also suggest that immune modulation induced by localized proton, as well as other forms of radiation, should be taken into consideration when evaluating adjunctive immunotherapies in patients receiving radiotherapy.