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

Robert E. Coles, Terrence J. Boyle, J. Michael DiMaio, Keith R. Berend, Dan F. Via, H. Kim Lyerly

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)405-410
Number of pages6
JournalAnnals of Surgical Oncology
Volume1
Issue number5
DOIs
StatePublished - Sep 1994

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Epstein-Barr Virus Infections
SCID Mice
Human Herpesvirus 4
B-Lymphocytes
T-Lymphocytes
Lymphocytes
Neoplasms
Leukocytes
Leukapheresis
Animal Diseases
Immunocompromised Host
Immunosuppressive Agents
Cyclosporine
Adrenal Cortex Hormones
Population

Keywords

  • B-Cell lymphoma
  • Epstein-Barr virus
  • Immunosuppression
  • Lymphomagenesis
  • Transplant lymphoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

T cells or active epstein-barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice. / Coles, Robert E.; Boyle, Terrence J.; DiMaio, J. Michael; Berend, Keith R.; Via, Dan F.; Kim Lyerly, H.

In: Annals of Surgical Oncology, Vol. 1, No. 5, 09.1994, p. 405-410.

Research output: Contribution to journalArticle

Coles, Robert E. ; Boyle, Terrence J. ; DiMaio, J. Michael ; Berend, Keith R. ; Via, Dan F. ; Kim Lyerly, H. / T cells or active epstein-barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice. In: Annals of Surgical Oncology. 1994 ; Vol. 1, No. 5. pp. 405-410.
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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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AU - Boyle, Terrence J.

AU - DiMaio, J. Michael

AU - Berend, Keith R.

AU - Via, Dan F.

AU - Kim Lyerly, H.

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N2 - 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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