Coles R E, Boyle T J, DiMaio J M, Berend K R, Via D F, Lyerly H K
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Ann Surg Oncol. 1994 Sep;1(5):405-10. doi: 10.1007/BF02303813.
Severe combined immunodeficient (SCID) mice develop Epstein-Barr virus (EBV) containing human lymphoproliferative disease (LPD) tumors when reconstituted with human peripheral blood leukocytes (PBLs) from EBV-seropositive donors, but LPD tumors do not develop in the presence of immunosuppressive agents, such as cyclosporine A or corticosteroids.
Therefore, LPD development in SCID mice was used as a model to explore the relationship among B cells, T cells, and EBV in vivo. SCID mice were engrafted with PBLs isolated by leukapheresis from a single EBV-seropositive donor. Purified populations of CD3+ lymphocytes (T cells) or CD19+ lymphocytes (B cells) were isolated and engrafted into SCID mice.
SCID mice engrafted with purified CD3+ lymphocytes (T cells) or CD19+ lymphocytes (B cells) did not develop LPD. In contrast, mice engrafted with purified B cells developed LPD if they were co-engrafted with purified T cells or if they were inoculated with infectious EBV.
This study confirms the requirement of T cells or active EBV infection in the development of LPD in animals engrafted with B cells latently infected with EBV. A greater understanding of the cellular and viral interactions leading to transformation and malignancy may allow the development of specific interventional therapies for malignancies in the immunosuppressed host.
严重联合免疫缺陷（SCID）小鼠在用人外周血白细胞（PBL）重建时，若供体为EBV血清反应阳性，则会发生含有EB病毒（EBV）的人类淋巴细胞增生性疾病（LPD）肿瘤，但在免疫抑制剂如环孢素A或皮质类固醇存在的情况下不会发生LPD肿瘤。
因此，将SCID小鼠中LPD的发生用作模型来探索体内B细胞、T细胞和EBV之间的关系。通过白细胞分离术从单个EBV血清反应阳性供体中分离出PBL移植到SCID小鼠体内。分离纯化的CD3+淋巴细胞（T细胞）或CD19+淋巴细胞（B细胞）群体，并移植到SCID小鼠体内。
移植了纯化的CD3+淋巴细胞（T细胞）或CD19+淋巴细胞（B细胞）的SCID小鼠未发生LPD。相反，移植了纯化B细胞的小鼠，如果与纯化T细胞共同移植或接种传染性EBV，则会发生LPD。
本研究证实了在移植有潜伏感染EBV的B细胞的动物中，LPD的发生需要T细胞或活跃的EBV感染。对导致转化和恶性肿瘤的细胞与病毒相互作用有更深入的了解，可能有助于开发针对免疫抑制宿主中恶性肿瘤的特异性干预疗法。
