Fu Y, Paul R D, Wang Y, Lopez D M
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
J Immunol. 1989 Dec 15;143(12):4300-7.
A profound thymic atrophy has been observed in mice bearing large adenocarcinomas of the mammary gland. Only 2 to 5% of thymocytes remained 4 wk after tumor implantation. Although there is a slight decrease in the overall percentages of Thy-1+ cells in tumor bearers, the majority of the remaining cells are of a Thy-1 low phenotype. There was a lower percentage of double positive (CD4+, CD8+) cells, an increase of CD4+ CD8- thymocytes, similar percentages of CD4- CD8+ cells and double negative (CD4- CD8-) thymocytes in tumor-bearing mice. In addition, an increased percentage of CD3 cells could be detected in these animals. These results indicate that proportionally less immature thymocytes are present in the atrophic thymuses of mammary tumor bearers. Enhanced levels of glucocorticoids are known to produce similar effects on the thymus. However, adrenalectomy of mice followed by tumor implantation did not result in reversal of the thymic atrophy. Furthermore, a study of serum corticosterone levels in tumor bearers indicated no significant changes during tumorigenesis. A study of several parameters of bone marrow (BM) populations indicate that there is an increase in cells of the granulocyte-macrophage lineage and a decrease in lymphocytes induced by tumor-derived granulocyte macrophage-CSF. An alteration of prothymocytes in the BM is not the main cause of the thymic atrophy because BM cells from normal and tumor-bearing mice reconstituted irradiated normal mice equally well. There was no preferential recruitment of double positive cells to the spleen as indicated by no significant differences in the levels of T cells of immature phenotype including the CD4+ CD8+ population in the spleens of tumor bearers. Because no major changes were observed in tumor bearers, either at their capacity to repopulate the thymus or at the patterns of subsequent redistribution of thymocytes, it was postulated that the thymic atrophy may be caused by a direct or indirect effect of the tumor or tumor-associated factor(s). Intrathymic injections of tumor cells into young normal recipient mice resulted in a significant reduction of the thymus weight and cellularity. These data suggest that mammary tumors can secrete factor(s) that are capable of severely impairing the normal development of cells of the T cell lineage.
在患有乳腺大腺癌的小鼠中观察到了严重的胸腺萎缩。肿瘤植入4周后，仅2%至5%的胸腺细胞留存。尽管荷瘤小鼠中Thy-1+细胞的总体百分比略有下降，但剩余细胞中的大多数具有Thy-1低表型。荷瘤小鼠中双阳性（CD4+、CD8+）细胞的百分比降低，CD4+ CD8-胸腺细胞增加，CD4- CD8+细胞和双阴性（CD4- CD8-）胸腺细胞的百分比相似。此外，在这些动物中可检测到CD3细胞的百分比增加。这些结果表明，在乳腺肿瘤荷瘤小鼠萎缩的胸腺中，未成熟胸腺细胞的比例相对较少。已知糖皮质激素水平升高会对胸腺产生类似影响。然而，对小鼠进行肾上腺切除术后再植入肿瘤，并未导致胸腺萎缩的逆转。此外，对荷瘤小鼠血清皮质酮水平的研究表明，在肿瘤发生过程中没有显著变化。对骨髓（BM）群体的几个参数进行的研究表明，肿瘤衍生的粒细胞巨噬细胞集落刺激因子可诱导粒细胞-巨噬细胞谱系的细胞增加，淋巴细胞减少。骨髓中前胸腺细胞的改变不是胸腺萎缩的主要原因，因为来自正常小鼠和荷瘤小鼠的骨髓细胞对受辐照的正常小鼠的重建效果相同。荷瘤小鼠脾脏中未成熟表型的T细胞水平，包括CD4+ CD8+群体，没有显著差异，这表明没有双阳性细胞优先募集到脾脏。由于在荷瘤小鼠中未观察到主要变化，无论是在其重新填充胸腺的能力方面，还是在随后胸腺细胞重新分布的模式方面，因此推测胸腺萎缩可能是由肿瘤或肿瘤相关因子的直接或间接作用引起的。向年轻正常受体小鼠胸腺内注射肿瘤细胞导致胸腺重量和细胞数量显著减少。这些数据表明，乳腺肿瘤可分泌能够严重损害T细胞谱系细胞正常发育的因子。
