Radiation damage and immune suppression in splenic mononuclear cell populations

Abstract

SUMMARY We have examined alterations in all of the major splenic mononuclear cell (SMNC) populations in C57Bl/6 mice following whole-body irradiation (0–700 cGy) in order to determine which populations may play a role in active immune suppression and/or haematopoietic recovery. A protocol has been established for characterization and differentiation by flow cytometric analysis (FCA) of the major MNC populations in the mouse spleen: T lymphocytes (CD4+ and CD8+ cells), B lymphocytes, natural killer (NK) cells, and monocytes/macrophages. Ionizing radiation caused decreased spleen cellularity and decreased ability of surviving SMNC to respond to mitogen. FCA revealed alterations in the relative composition of the constituent splenic cell populations following irradiation, reflecting differential radiosensitivity, with selective enrichment of NK cells (seven-fold) and CD4+ T lymphocytes (three-fold). Enrichment developed during the 7-day post-irradiation period. In addition, some MNC became activated in a dose- and time-dependent fashion following whole-body irradiation, as indicated by expression of CD71, the transferrin receptor. These cells were CD34+ and Thy1.2+, but were CD4− or CD8− as well as CD45− (B cell). The observed increase in NK cells corresponds with a previously reported increase in natural suppressor (NS) cells following total-lymphoid irradiation (TLI). The balance of recovery-inhibiting NK cells and recovery-enhancing CD4+ T lymphocytes following irradiation may reflect or influence the degree of haematopoietic recovery, and may provide an indication of the extent of damage (biological dosimetry).