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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 2999-3006
Allo-Major Histocompatibility Complex-Restricted
Cytotoxic T Lymphocytes Engraft in Bone Marrow Transplant Recipients
Without Causing Graft-Versus-Host Disease
Liquan Gao,
Tian-Hui Yang,
Sophie Tourdot,
Elena Sadovnikova,
Robert Hasserjian, and
Hans J. Stauss
From the Departments of Immunology and of Histopathology, Imperial
College School of Science Technology and Medicine, Hammersmith
Hospital, London, UK.
Previous experiments in humans and mice have shown that allogeneic
donors can serve as a source of cytotoxic T lymphocytes (CTL) specific
for proteins, such as cyclin-D1 and mdm-2, expressed at elevated levels
in tumor cells. In vitro, allo-major histocompatibility complex
(MHC)-restricted CTL against these proteins selectively killed allogeneic tumor cells, including lymphoma, but not normal control cells. This suggested that these CTL may be useful for adoptive
tumor immunotherapy, provided that they (1) survive in MHC-disparate
hosts, (2) maintain their killing specificity, and (3) do not attack
normal host tissues. Here, we used cloned allo-restricted CTL isolated
from BALB/c mice (H-2d) that killed
H-2b-derived tumor cells expressing elevated levels of the
mdm-2 target protein. When these CTL were injected into bone marrow
transplanted (BMT) C57BL/6 (H-2b) recipients, they
consistently engrafted and were detectable in lymphoid tissues and in
the bone marrow (BM). Long-term survival was most efficient in spleen
and lymph nodes, where CTL were found up to 14 weeks after injection.
The administration of CTL did not cause graft-versus-host disease
(GVHD) normally associated with injection of allogeneic T cells. These
data show that allo-restricted CTL clones are promising reagents for
antigen-specific immunotherapy in BMT hosts, because they engraft and
retain their specific killing activity without causing GVHD.
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