Evaluation for synergistic suppression of T cell responses to minor histocompatibility antigens by chloroquine in combination with tacrolimus and a rapamycin derivative, SDZ-RAD
| Autor: | Hsiao Cc, Andrew L. Gilman, Farzin Forooghian, Rempel J, Bader S, Kent T. HayGlass, Kirk R. Schultz, Su Wn |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
T-Lymphocytes
medicine.medical_treatment Lymphocyte T cell Drug Evaluation Preclinical Graft vs Host Disease Apoptosis Pharmacology Lymphocyte Activation Tacrolimus Minor Histocompatibility Antigens Mice Chloroquine Minor histocompatibility antigen Animals Humans Medicine Everolimus Antigen-presenting cell Cells Cultured Sirolimus Antigen Presentation Mice Inbred BALB C Transplantation business.industry Drug Synergism Hematology Immunotherapy Recombinant Proteins T cell cytokine production Mice Inbred C57BL surgical procedures operative medicine.anatomical_structure Immunology Cytokines Interleukin-2 Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Bone Marrow Transplantation. 30:905-913 |
| ISSN: | 1476-5365 0268-3369 |
| DOI: | 10.1038/sj.bmt.1703727 |
| Popis: | 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-CD3epsilon 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. |
| Databáze: | OpenAIRE |
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