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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3083-3088
PLENARY PAPER
Prevention of graft-versus-host disease while preserving
graft-versus-leukemia effect after selective depletion of host-reactive
T cells by photodynamic cell purging process
Benny J. Chen,
Xiuyu Cui,
Congxiao Liu, and
Nelson J. Chao
From the Bone Marrow Transplantation Program, Duke
University Medical Center, Durham, NC.
In this study, we investigated the possibility of selective
depletion of donor alloantigen-specific T cells from C57BL/6
(H-2b) mice to prevent graft-versus-host disease (GVHD).
These cells were first activated with irradiated BALB/c
(H-2d) host spleen cells in a 5-day mixed lymphocyte
culture. Following this activation, a photoactive rhodamine derivative
called 4,5-dibromorhodamine 123 (TH9402), was added. This compound is
selectively retained in the mitochondria of activated host-reactive
cells but not tumor- or third-party-specific resting cells. The
treated cells were subsequently exposed to visible light (514 nm) to
deplete the TH9402-enriched activated host-reactive cells. Treatment
with photodynamic cell purging process (PDP) inhibited antihost
responses measured by cytotoxic T lymphocytes (CTL) by 93%, and
interferon- production by 66%. By contrast, anti-BCL1
(BALB/c-origin leukemia/lymphoma) and anti-third-party C3H/HeJ
(H-2k) responses were preserved. PDP-treated primed C57BL/6
cells were further tested in vivo. All lethally irradiated BALB/c mice
inoculated with BCL1 cells and T-cell-depleted bone marrow cells
developed leukemia by day +30, with 50% mortality by 100 days. All
mice died of GVHD after addition of 5 × 106
untreated primed C57BL/6 cells. However, addition of same numbers of PDP-treated cells allowed 90% of the recipients to
survive more than 100 days without detectable BCL1 tumor cells and
free of GVHD. Moreover, PDP-treated primed C57BL/6 cells retained the ability to induce GVHD in the third-party C3H/HeJ mice. These data
suggest that PDP can selectively deplete host alloantigen-specific T
cells for GVHD prevention and immune and antileukemia function preserve.
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