Fetal thymic atrophy after exposure to T-2 toxin: selectivity for lymphoid progenitor cells.

Treatment of experimental animals with T-2 toxin has been found to markedly decrease thymic cellularity and to suppress cell-mediated immune function. Although T-2 toxin readily crosses the placenta, little is known about its effect on development of immunity following gestational exposure. In the present report, prenatal T-2 toxin resulted in significant fetal thymic atrophy in mice. In vitro exposure to T-2 toxin resulted in decreased thymocyte proliferation, as well as significant but transient increases in thymocyte viability. Cycloheximide increased thymocyte viability parallel to that seen after T-2 toxin, indicating that enhanced viability after T-2 toxin may be the result of inhibited endonuclease synthesis. These findings suggest that direct cytotoxic effects of T-2 toxin make limited contribution to thymic atrophy production. In support of this conclusion, in vivo T-2 toxin exposure resulted in only limited alteration of thymocyte development, as evidenced by expression of CD4, CD8, and alpha beta TCR cell-surface antigens. These data further indicate that antiproliferative effects of T-2 toxin on thymocytes may contribute limitedly to thymic atrophy observed in vivo. In vivo T-2 toxin treatment did not affect total numbers of CD44+, CD45+, or Mac-1+ fetal liver cells. However, such exposure resulted in significant decreases in CD44lo and CD45lo fetal liver prolymphoid cell subpopulations. Subsequent in vitro T-2 toxin exposure of fetal liver cells enriched for lymphoid precursors resulted in both decreased cell viability and highly significant decreased proliferation. Taken together, these data suggest that lymphocyte progenitors, in contrast to thymocytes, represent highly sensitive targets of T-2 toxin exposure, responsible for thymic atrophy.