B-LYMPHOCYTE PRECURSOR CELLS REPRESENT SENSITIVE TARGETS OF T2 MYCOTOXIN EXPOSURE

Exposure of experimental animals and humans to the Fusarium trichothec ene metabolite, T2 toxin, has been associated with a variety of immuno suppressive 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 contributio n of such a mechanism to immunosuppression in vivo, or to potential im mune cell targets. In the present report, subchronic T2 toxin treatmen t of timed-pregnant B6C3F1 mice resulted in significant and selective depletion of fetal liver cells expressing low levels of surface CD44 a nd CD45 antigens, suggestive of possible lymphoid progenitor cell sens itivity to this agent. Evaluation of CD45R antigen expression in fetal liver supported such a hypothesis, demonstrating a significant reduct ion in fetal liver B lymphocytic cells in animals exposed to T2 toxin. Subsequent in vitro T2 toxin exposure of fetal liver cells enriched f or prolymphocytes by differential density gradient centrifugation demo nstrated the presence of a highly sensitive subpopulation of cells tha t was eliminated in a selective, and near-complete, manner by T2 toxin exposure. This sensitive cell population was observed to have light-s catter characteristics of CD45R(+) B-lineage lymphocytes. Additional s tudies in adult mice demonstrated a reduction in CD44(lo) and CD45R(+) bone marrow cells similar to that seen in fetal liver, indicating tha t T2 toxin may also target immature B lymphocytes in this hematopoieti c compartment. Taken together, these data suggest that the precursors of B cells may represent, for unknown reasons, highly sensitive target s of T2 toxin exposure. (C) 1995 Academic Press, Inc.