title: Irinotecan combined with co-stimulatory molecule blockade prolongs survival of cardiac allografts in alloantigen-primed mice.
abstract: Memory T cells play an important role in graft rejection. In this study, we investigated the potential effect of Irinotecan (CPT-11), a topoisomerase I inhibitor used in the treatment of a variety of solid tumor malignancies, on memory T cells. CPT-11 treatment alone or combined with blocking monoclonal antibodies (mAb) against co-stimulatory molecules (LFA-1 and CD154) was evaluated in the prevention of heart transplant rejection in alloantigen-primed mice. Our data suggest that CPT-11 reduced the expression of IL-2/IFN-γ and increased IL-10/TGF-β expression in both peripheral blood and within the grafts. CPT-11 could also inhibit alloresponses of memory T cells, while decreasing the proportion of CD4(+) memory T cells in the spleen of the recipients and significantly reducing serum alloantibody levels. Our study highlights obvious synergistic effects of CPT-11 when combined with co-stimulatory molecule blockade in prolonging the survival of cardiac allografts in alloantigen-primed mice.
authors.affiliation: Organ Transplantation Institute, Xiamen University, Fujian Province 361000, PR China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Chen
authors.forename: Ruwen
authors.initials: R
authors.lastname: Yang
authors.forename: Jibing
authors.initials: J
authors.lastname: Chen
authors.forename: Panpan
authors.initials: P
authors.lastname: Cheng
authors.forename: Zongnan
authors.initials: Z
authors.lastname: He
authors.forename: Zhongchen
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D023201:CD40 Ligand / Q000276:immunology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000379:methods*; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics / Q000276:immunology; D000077146:Irinotecan; D007519:Isoantigens / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D023201:CD40 Ligand; D000077146:Irinotecan; D007371:Interferon-gamma; D002166:Camptothecin
keywords: Alloantigen-primed mice; Irinotecan; Memory T cells