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Surgery. 1993 Aug;114(2):218-25; discussion 226.

Adoptive transfer of cytotoxic T lymphocytes for the treatment of transplant-associated lymphoma.

Author information

1
Department of Surgery, Duke University Medical Center, Durham, NC 27710.

Abstract

BACKGROUND:

Immunocompromised organ transplant recipients have a high incidence of B cell lymphomas (BCL). Severe combined immunodeficient (SCID) mice develop human BCL when engrafted with Epstein-Barr virus (EBV) transformed and immortalized B lymphoblastoid cell lines (BLCL). Because a lack of effective EBV-specific cytotoxic T lymphocytes (EBV-CTL) is thought to lead to lymphoma development, the SCID mouse model was used to determine the relationship between EBV-infected B cells and EBV-specific CTL in BCL development in vivo.

METHODS:

EBV-CTL were generated by in vitro stimulation of peripheral blood leukocytes with autologous BLCL. CD8+ CTL were isolated from CTL populations by depletion of CD4+ cells. SCID mice were engrafted with BLCL, EBV-CTL were adoptively transferred into engrafted SCID mice either immediately or 7 days after engraftment, and the animals were monitored for the development of BCL. Statistical significance was determined by the log rank test.

RESULTS:

SCID mice engrafted with BLCL rapidly developed BCL (mean, 20 days). SCID mice engrafted with BLCL and human leukocyte antigen-identical EBV-CTL or CD8+ EBV-CTL had a significant delay in BCL development (p < 0.05), whereas some mice did not develop BCL. In contrast, human leukocyte antigen-nonidentical EBV-CTL did not significantly delay BCL development.

CONCLUSIONS:

This study showed the role of EBV-CTL in inhibiting the development of BCL. A greater understanding of the cellular and viral interactions leading to B-cell transformation and malignancy may allow the development of specific interventional therapies in patients who have received immunosuppressants.

PMID:
8393595
[Indexed for MEDLINE]

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