T cells or active Epstein-Barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice

• Published in: Annals of surgical oncology 1994-09, Vol.1 (5), p.405-410
• Main Authors: Coles, R E, Boyle, T J, DiMaio, J M, Berend, K R, Via, D F, Lyerly, H K
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD19; Antigens, Differentiation, B-Lymphocyte - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; B-Lymphocytes - transplantation; CD3 Complex - immunology; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - pathology; Cell Transplantation; Flow Cytometry; Herpesviridae Infections - immunology; Herpesviridae Infections - pathology; Herpesviridae Infections - virology; Herpesvirus 4, Human; Humans; Injections; Lymphoproliferative Disorders - immunology; Lymphoproliferative Disorders - pathology; Lymphoproliferative Disorders - virology; Mice; Mice, SCID; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Tumor Virus Infections - immunology; Tumor Virus Infections - pathology; Tumor Virus Infections - virology
• ISSN: 1068-9265; 1534-4681
• 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.