Shanker A, Singh S M
Center of Immunology Marseille-Luminy, CNRS-INSERM-Mediteranian University, Marseille, 13288 France.
Neoplasma. 2003;50(4):272-9.
Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. Moreover, an inhibition of humoral and cell mediated immune responses involving non-specific as well as antigen-specific T cell proliferative and cytolytic abilities with a decrease in the production of interferon gamma (IFNg) by the T cells of DL bearing mice has been observed. Results of the present study show that the administration of total thymic extract (TE) in DL bearing mice results in an increased survival of the DL bearing mice alongwith a significant increase in the weight of thymus and the total number of thymocytes with a lesser number of percent apoptotic thymocytes as compared to that in untreated DL-bearing mice. It is also shown that TE administration has a positive immunomodulatory effect on T cell functions as T cells obtained from TE administered DL bearing mice show an increased IFNg, production and an improved antigen specific proliferative ability. Moreover, the study indicates that TE acts directly on T cells as in an in vitro assay TE antagonised DL growth-associated induction of thymocyte apoptosis. Taken together, the results support the immunomodulatory function of the adult thymus and utilization of thymus derived factors as a potential immunotherapeutic agent for reversing tumor growth-associated immunosuppression.
在鼠宿主中，一种名为道尔顿淋巴瘤（DL）的自发性可移植T细胞淋巴瘤的进行性腹水生长已被证明与胸腺退化有关，胸腺退化伴有皮质区域的大量消耗以及胸腺细胞分布的改变，这是由于胸腺细胞凋亡诱导增强导致CD4+CD8+、CD4+CD8-和CD4-CD8+表型减少所致。此外，还观察到涉及非特异性以及抗原特异性T细胞增殖和细胞溶解能力的体液和细胞介导免疫反应受到抑制，携带DL的小鼠的T细胞产生的干扰素γ（IFNγ）减少。本研究结果表明，给携带DL的小鼠施用全胸腺提取物（TE）可提高携带DL的小鼠的存活率，同时胸腺重量和胸腺细胞总数显著增加，与未治疗的携带DL的小鼠相比，凋亡胸腺细胞的百分比更低。还表明，TE给药对T细胞功能具有积极的免疫调节作用，因为从施用TE的携带DL的小鼠获得的T细胞显示IFNγ产生增加且抗原特异性增殖能力提高。此外，该研究表明TE直接作用于T细胞，因为在体外试验中，TE拮抗了与DL生长相关的胸腺细胞凋亡诱导。综上所述，这些结果支持成年胸腺的免疫调节功能以及利用胸腺衍生因子作为逆转肿瘤生长相关免疫抑制的潜在免疫治疗剂。
