title: Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation.
abstract: CD4(+)CD25(+) forkhead box P3 (FoxP3)(+)regulatory T (T(reg)) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and T(reg) cells. Basiliximab (Simulect), a chimeric monoclonal antibody directed against the alpha-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of T(reg) cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the T(reg) cells in renal recipients. Basiliximab decreased the percentage of CD4(+)CD25(+)T cells, but failed to influence the percentage of CD4(+)FoxP3(+) T(reg) cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4(+)CD25(+) T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of T(reg) cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional T(reg) population may not be influenced by short-term basiliximab treatment.
authors.affiliation: The Organ Transplant Center, The Second Affiliated Hospital of the Chinese Peoples Liberation Army (PLA) General Hospital, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: B-Y
authors.initials: BY
authors.lastname: Shi
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Qian
authors.forename: M
authors.initials: M
authors.lastname: Cai
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D015415:Biomarkers / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000276:immunology; D015870:Gene Expression; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D000077552:Basiliximab