Holladay S D, Blaylock B L, Comment C E, Heindel J J, Luster M I
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg 24061-0442.
Toxicol Appl Pharmacol. 1993 Jul;121(1):8-14. doi: 10.1006/taap.1993.1122.
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.
已发现用T-2毒素处理实验动物可显著降低胸腺细胞数量并抑制细胞介导的免疫功能。尽管T-2毒素很容易穿过胎盘，但关于其在孕期暴露后对免疫发育的影响却知之甚少。在本报告中，产前接触T-2毒素导致小鼠胎儿胸腺显著萎缩。体外接触T-2毒素导致胸腺细胞增殖减少，以及胸腺细胞活力显著但短暂增加。环己酰亚胺使胸腺细胞活力增加的情况与T-2毒素处理后相似，表明T-2毒素处理后活力增强可能是内切核酸酶合成受抑制的结果。这些发现表明，T-2毒素的直接细胞毒性作用对胸腺萎缩的产生贡献有限。支持这一结论的是，体内接触T-2毒素仅导致胸腺细胞发育发生有限改变，这可通过CD4、CD8和αβTCR细胞表面抗原的表达得到证明。这些数据进一步表明，T-2毒素对胸腺细胞的抗增殖作用可能对体内观察到的胸腺萎缩贡献有限。体内T-2毒素处理不影响CD44+、CD45+或Mac-1+胎儿肝细胞的总数。然而，这种接触导致CD44lo和CD45lo胎儿肝前淋巴细胞亚群显著减少。随后对富含淋巴细胞前体的胎儿肝细胞进行体外T-2毒素接触，导致细胞活力下降和增殖显著降低。综上所述，这些数据表明，与胸腺细胞不同，淋巴细胞祖细胞是T-2毒素接触的高度敏感靶点，是胸腺萎缩的原因。
