Binhazim A A, Rizvi T A, Coghlan L G, Lew K, Schmidt R, Wong P K
Department of Veterinary Sciences, University of Texas M.D. Anderson Cancer Center, Bastrop 78602, USA.
Lab Invest. 1996 Sep;75(3):339-48.
By serving as host recipients of xenografts from both humans and animals, severe combined immunodeficient (SCID) mice have become valuable to many laboratories interested in examining the pathophysiology of different diseases. To gain insight into the usefulness of the SCID mutation in retrovirus research, rhesus monkey fetal hematolymphoid tissues (liver and thymus) were used to construct a SCID-rhesus chimeric mouse (SCID-rh) and were engrafted in the renal capsule. The size and maturation of the thymic engrafts were monitored grossly, histologically, and immunologically. SCID mice were tolerant to rhesus tissues, and thymic engrafts contained thymocytes at different stages of maturation and differentiation that had morphologic features similar to age-matched rhesus thymus. Mature single positive CD2+, CD4+, and CD8+ T lymphocytes that were phenotypically similar to rhesus T lymphocytes were present at low levels (2% to 5%) in the peripheral blood and at moderately higher levels (7% to 15%) in the spleens of SCID-rh mice obtained between 12 and 15 weeks after thymus/liver engraftment. Within 3 weeks after engraftment, > 85% of the thymocytes in the thymic engrafts were immature double positive CD4+CD8+ T cells. The highest number of positive cells were seen in thymic engrafts obtained at 12 to 18 weeks. During these weeks, > 90% of the cells were double positive (CD2+CD4+, CD2+CD8+, and CD4+CD8+). After infection of the engrafted thymus tissue with simian immonodeficiency virus (SIVmac239), PCR analysis revealed successful viral infection of engrafts at 2 and 4 weeks after infection. No significant histopathologic and flow cytometric changes were observed in the thymic engrafts at 2 and 4 weeks after infection. An unrelated lesion of thymic lymphomas involving the SCID host thymus was seen in 12% of the mice. The data presented herein suggest that the SCID-rh is a valuable model for specific studies related to thymus-retrovirus interaction and that it could be used for further studies. The results are discussed in relation to current knowledge of thymus involvement during simian and human immunodeficiency virus infection.
作为人类和动物异种移植物的宿主受体，严重联合免疫缺陷（SCID）小鼠对于许多致力于研究不同疾病病理生理学的实验室来说变得非常有价值。为了深入了解SCID突变在逆转录病毒研究中的作用，使用恒河猴胎儿造血淋巴组织（肝脏和胸腺）构建了SCID-恒河猴嵌合小鼠（SCID-rh），并将其植入肾被膜。通过大体观察、组织学检查和免疫学方法监测胸腺植入物的大小和成熟情况。SCID小鼠对恒河猴组织具有耐受性，胸腺植入物中含有处于不同成熟和分化阶段的胸腺细胞，其形态特征与年龄匹配的恒河猴胸腺相似。在胸腺/肝脏植入后12至15周获得的SCID-rh小鼠的外周血中，表型与恒河猴T淋巴细胞相似的成熟单阳性CD2 +、CD4 +和CD8 + T淋巴细胞水平较低（2%至5%），而在脾脏中的水平略高（7%至15%）。植入后3周内，胸腺植入物中>85%的胸腺细胞为未成熟双阳性CD4 + CD8 + T细胞。在12至18周获得的胸腺植入物中观察到阳性细胞数量最多。在这些周内，>90%的细胞为双阳性（CD2 + CD4 +、CD2 + CD8 +和CD4 + CD8 +）。在用猿猴免疫缺陷病毒（SIVmac239）感染植入的胸腺组织后，PCR分析显示感染后2周和4周植入物成功发生病毒感染。感染后2周和4周，胸腺植入物中未观察到明显的组织病理学和流式细胞术变化。在12%的小鼠中发现了涉及SCID宿主胸腺的无关胸腺淋巴瘤病变。本文提供的数据表明，SCID-rh是用于胸腺-逆转录病毒相互作用相关特定研究的有价值模型，可用于进一步研究。结合目前关于猿猴和人类免疫缺陷病毒感染期间胸腺参与情况的知识对结果进行了讨论。
