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Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice:
requirement for a human lymphoid microenvironment
EK Waller, OW Kamel, ML Cleary, AS Majumdar, MR Schick, M Lieberman and IL Weissman
Department of Medicine, Stanford University Medical Center, CA 94305- 5468.
We reasoned that the SCID-hu mouse could provide an appropriate lymphoid or
stromal microenvironment to support the growth of primary human lymphoma.
Heterotransplantation of nine cases of primary T-cell non-Hodgkin's
lymphoma (NHL) into untreated SCID mice and SCID mice reconstituted with
human fetal thymus, spleen, and liver (SCID-hu) resulted in the development
of lymphoid tumors in five (56%) cases. Two clonal T-cell NHL grew after a
mean of 90 days after injection of primary lymphoma cell suspensions into
the thymus xenografts in SCID-hu mice and failed to grow in a variety of
sites in SCID mice, except for small tumors that developed after a long
(157-day) latency period after intracranial injection of tumor cell
suspensions into weanling SCID mice. Successful serial transplantation of
NHL in SCID and SCID-hu mice required the presence of a human lymphoid or
tumor microenvironment, and was enhanced by pretreating the SCID mice with
175 rad radiation and antiasialo antisera. Analysis of the primary and
transplanted T- cell tumors showed identical patterns of T-cell surface
markers by flow cytometry and immunophenotyping of fixed tissue sections,
and, in one case, reactivity with a specific monoclonal antibody to V beta
5.1. Genotyping of the transplanted tumors showed T-cell receptor gene
rearrangements identical to those present in the primary tumors. In one
case, the presence of Epstein-Barr virus-positive B cells in association
with the primary tumor resulted in the growth of a lymphoblastoid B-cell
neoplasm in addition to the malignant T-cell lymphoma after transplantation
of tumor fragments to SCID mice. The data support the hypothesis that a
human lymphoid microenvironment enhances the growth of T-cell NHL in SCID
mice. The SCID-hu thymus graft provides an apparently unique
microenvironment that supports the growth of primary T-cell NHL, and can be
used to study the interaction between lymphoma cells, nontransformed
lymphoid cells, and the surrounding stromal microenvironment in vivo.
Volume 78,
Issue 10,
pp. 2650-2665,
11/15/1991
Copyright © 1991 by The American Society of Hematology
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