Characterization of Rabbit Antithymocyte Globulins-Induced CD25+ Regulatory T Cells From Cells of Patients With End-Stage Renal Disease

• DOI: 10.1097/tp.0b013e3181c9cc7a
• Publication Date: 2010-03-15T18:49:21Z
• Authors: Varsha D. K. D. S...; Luc J. W. van der...; Marcia M. L. Kho; Rens Kraaijeveld; Sander S. Korevaar; Thea van Dam; Jan N. M. Ijzermans; Willem Weimar; Carla C. Baan
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; EMC MM-04-20-02-A; EMC MM-04-39-05; Dose-Response Relationship, Immunologic; EMC MM-04-20-01; EMC MM-04-47-07; Granzymes; Immunophenotyping; Interleukin-7 Receptor alpha Subunit; 03 medical and health sciences; Animals; Humans; Cells, Cultured; Antilymphocyte Serum; EMC MM-03-47-02-A; Perforin; Interleukin-2 Receptor alpha Subunit; Forkhead Transcription Factors; Flow Cytometry; Kidney Transplantation; 3. Good health; Phenotype; Case-Control Studies; Leukocytes, Mononuclear; Cytokines; Kidney Failure, Chronic; Protein Binding

BACKGROUND.: Rabbit antithymocyte globulins (rATGs) are known to convert CD4CD25FoxP3 T cells from healthy individuals cells. In this study, we investigated the effect of rATG on induction regulatory (Tregs) blood patients with end-stage renal disease who candidates for transplantation and rATG-induction therapy. The induced Tregs were analyzed compared naturally occurring CD4CD25FoxP3T METHODS.: CD25 pretransplant (n=7) controls (n=4) stimulated or control rabbit immunoglobulins 24 hr. phenotype was examined by flow cytometry, their function studied in conventional suppression assay. Further characterization performed mRNA analyses. RESULTS.: After hr, percentage CD4CD25FoxP3CD127 CD8CD25FoxP3CD127 became higher rATG-treated samples immunoglobulin-treated (P<0.01). rATG-induced CD25T cells, whether CD4 CD8 inhibited allogeneic responses effector as vigorously natural However, proportion FoxP3 within top 2% CD4CD25T-cells lower than (11%+/-2% vs. 95%+/-5%, P<0.01). mRNA-expression levels interleukin-27, interleukin-10, interferon-gamma, perforin, granzyme B markedly CD25T-cells (all P=0.03), whereas CTLA4 (P=0.03), transforming growth factor-beta (P=0.02), RORgammat (P=0.04) lower. CONCLUSION.: allows patient peripheral mononuclear cell vitro. comparison Tregs, phenotypically distinct but have similar activities. may beneficially contribute mechanisms that alloreactivity.