Single dose of 5 Gy can damage erythrocytes and consequently induces lymphocyte depletion in spleen and circulating blood.

Purpose: Radiation-induced lymphopenia (RIL) has been well known to associate with poor patient prognosis. Based on interesting findings in our previous study, we hypothesize that a low dose of 5-Gy can damage erythrocytes, which indirectly depletes lymphocytes in spleen, and may contribute to RIL. This study aimed to verify the hypothesis. Methods: Rats were divided into non-irradiated and 5Gy-irradiated groups. Peripheral blood was collected. Erythrocytes were isolated, irradiated for the irradiated group, and transfused back into the same rat for both groups. Peripheral blood samples were collected at different timepoints post-transfusion for analysis. At 72-hour timepoint, peripheral blood and spleen tissues were collected for flow cytometric analysis and histopathological examination. Morphological changes of irradiated erythrocytes were also studied. Results: Irradiation of 5-6 Gy could damage erythrocytes in a degree, as demonstrated by morphological changes after radiation. Irradiated and transfused erythrocytes were recognized and phagocytosed in spleen, as demonstrated by significantly increasing hemosiderin-laden macrophages presented in the red pulp. Cytometric analysis and complete blood count analysis showed that the clearing process depleted B lymphocytes in peripheral blood, and both T and B lymphocytes in spleen. Conclusions: This exploratory study suggests that low-dose irradiated erythrocytes can be recognized and cleared in spleen, and that this process is associated with marked lymphocyte depletion in both the spleen and peripheral blood.