B lymphocyte precursor cells represent sensitive targets of T2 mycotoxin exposure

Exposure of experimental animals and humans to the Fusarium trichothecene metabolite, T2 toxin, has been associated with a variety of immunosuppressive effects, including altered parameters of humoral-mediated immunity. Although T2 toxin is cytotoxic in vitro to lymphocytic cells, limited information is presently available regarding the contribution of such a mechanism to immunosuppression in vivo, or to potential immune cell targets. In the present report, subchronic T2 toxin treatment of timed-pregnant B6C3F1 mice resulted in significant and selective depletion of fetal liver cells expressing low levels of surface CD44 and CD45 antigens, suggestive of possible lymphoid progenitor cell sensitivity to this agent. Evaluation of CD45R antigen expression in fetal liver supported such a hypothesis, demonstrating a significant reduction in fetal liver B lymphocytic cells in animals exposed to T2 toxin. Subsequent in vitro T2 toxin exposure of fetal liver cells enriched for prolymphocytes by differential density gradient centrifugation demonstrated the presence of a highly sensitive subpopulation of cells that was eliminated in a selective, and near-complete, manner by T2 toxin exposure. This sensitive cell population was observed to have light-scatter characteristics of CD45R+ B-lineage lymphocytes. Additional studies in adult mice demonstrated a reduction in CD44lo and CD45R+ bone marrow cells similar to that seen in fetal liver, indicating that T2 toxin may also target immature B lymphocytes in this hematopoietic compartment. Taken together, these data suggest that the precursors of B cells may represent, for unknown reasons, highly sensitive targets of T2 toxin exposure.