T cells or active Epstein-Barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice.
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 infectious 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.
Coles
R E
RE
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Boyle
T J
TJ
DiMaio
J M
JM
Berend
K R
KR
Via
D F
DF
Lyerly
H K
HK
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D017252:CD3 Complex / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000473:pathology; D017690:Cell Transplantation; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007267:Injections; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014412:Tumor Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D017252:CD3 Complex