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Immune Suppression

Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD

Bone Marrow Transplantation volume 30, pages 905–913 (2002)Cite this article

Abstract

The 4-aminoquinolines, chloroquine and hydroxychloroquine, can suppress chronic graft-versus-host disease (GVHD) following blood and marrow transplantation (BMT) in mice and humans, respectively. We hypothesized that chloroquine in combination with tacrolimus and the rapamycin derivative SDZ-RAD can synergistically suppress T cell responses and antigen-presenting cell (APC) function in vitro. We used the APC-dependent C57BL/6 anti-BALB.B T cell response and APC-independent anti-CD3ε antibody-induced response to evaluate the role of synergism between chloroquine and tacrolimus or SDZ-RAD on each component of a T cell response to minor histocompatibility antigens. We found that chloroquine with tacrolimus had a greater synergistic suppression of APC-dependent compared to the APC-independent T cell responses, with a combination index (CIx) for 50% inhibition by mean effect analysis of 0.16 and 0.50, respectively (a lower number indicates greater suppression). By contrast, chloroquine with SDZ-RAD had a similar CIx between the two responsed 0.50 vs0.45) suggesting only T cell suppression. Synergy between chloroquine and SDZ-RAD involved a direct effect on T cell cytokine production, whereas synergism between chloroquine and tacrolimus was due to an effect on both T cells and APCs. We conclude that the renal-sparing 4-aminoquinolines may be used syneristically with immunosuppressive drugs currently used for BMT.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Chang Gung Children's Hospital, Kaohsiung, Taiwan, ROC

    C-C Hsiao

  2. Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, University of British Columbia and BC's Children's Hospital, Vancouver, BC, Canada

    WN Su, F Forooghian, S Bader & KR Schultz

  3. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada

    J Rempel & KT HayGlass

  4. Children's Mercy Hospital, Kansas City, MO, USA

    A Gilman

Authors
  1. C-C Hsiao
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  2. WN Su
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  3. F Forooghian
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Hsiao, CC., Su, W., Forooghian, F. et al. Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD. Bone Marrow Transplant 30, 905–913 (2002). https://doi.org/10.1038/sj.bmt.1703727

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  • DOI: https://doi.org/10.1038/sj.bmt.1703727

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