Immunological advantages of everolimus versus cyclosporin A in liver‐transplanted recipients, as revealed by polychromatic flow cytometry

Cytometry. Part A : the journal of the International Society for Analytical Cytology - Tập 81A Số 4 - Trang 303-311 - 2012
Erika Roat1, Sara De Biasi1, Linda Bertoncelli1, Gianluca Rompianesi2, Milena Nasi1, Lara Gibellini1, Marcello Pinti1, Cinzia Del Giovane3, Andrea Zanella4, Fabrizio Di Benedetto2, Giorgio Enrico Gerunda2, Andrea Cossarizza5
1Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy
2Liver and Multivisceral Transplant Center, Azienda Ospedaliero‐Universitaria Policlinico di Modena, Modena 41124, Italy
3Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena 41124, Italy
4General Management Division, Becton Dickinson Biosciences Italy, 20090 Buccinasco, Milano, Italy
5Department of Biomedical Sciences, University of Modena and Reggio Emilia, via Campi 287, Modena 41125, Italy

Tóm tắt

AbstractSeveral immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver‐transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)‐2 and interferon (IFN)‐γ, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4+ and naïve CD4+ T cells than those treated with CsA; the percentage of CD8+ T cells was lower, but the frequency of naïve CD8+ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8+ T cells from Evr‐treated patients displayed a lower total response, and less IFN‐γ producing cells. The effects on the immune system, such as the preservation of the naïve T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages. © 2012 International Society for Advancement of Cytometry

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Cytometry. Part A : the journal of the International Society for Analytical Cytology

Tập 81A Số 4

303-311

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