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

Blood - Tập 99 - Trang 3083-3088 - 2002
Benny J. Chen1, Xiuyu Cui1, Congxiao Liu1, Nelson J. Chao1
1From the Bone Marrow Transplantation Program, Duke University Medical Center, Durham, NC.

Tóm tắt

Abstract

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-γ 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 × 106untreated 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.


Tài liệu tham khảo

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Blood

Tập 99

3083-3088

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