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.

Abstract

In this study, we investigated the possibility of selective depletion of donor alloantigen-specific T cells from C57BL/6 (H-2(b)) mice to prevent graft-versus-host disease (GVHD). These cells were first activated with irradiated BALB/c (H-2(d)) 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-gamma production by 66%. By contrast, anti-BCL1 (BALB/c-origin leukemia/lymphoma) and anti-third-party C3H/HeJ (H-2(k)) 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 x 10(6) 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.

• Authors: Benny J Chen, Xiuyu Cui, Congxiao Liu, Nelson J Chao
• Journal: Blood (Blood) Vol. 99 Issue 9 Pg. 3083-8 (May 01 2002) ISSN: 0006-4971 [Print] United States
• PMID: 11964269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents
• Rhodamines
• 4,5-dibromorhodamine 123

Topics

• Animals
• Bone Marrow Transplantation (methods)
• Female
• Graft vs Host Disease (prevention & control)
• Graft vs Leukemia Effect (radiation effects)
• Histocompatibility (radiation effects)
• Light
• Lymphocyte Depletion (methods)
• Mice
• Mice, Inbred Strains
• Photosensitizing Agents (pharmacology)
• Rhodamines (pharmacology)
• T-Lymphocytes (immunology, radiation effects)
• T-Lymphocytes, Cytotoxic (cytology)
• Transplantation Immunology (radiation effects)
• Tumor Cells, Cultured