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

RE Coles, TJ Boyle, JM DiMaio, KR Berend… - Annals of surgical …, 1994 - Springer
RE Coles, TJ Boyle, JM DiMaio, KR Berend, DF Via, H Kim Lyerly
Annals of surgical oncology, 1994Springer
Background: 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. Methods: 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 …
Abstract
Background: 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.
Methods: 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.
Results: 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 infections EBV.
Conclusions: 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.
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