title: Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion.
abstract: T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naive T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant.
authors.affiliation: Transplantation Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Pearl
authors.forename: Jeremy
authors.initials: J
authors.lastname: Parris
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hale
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hoffmann
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bernstein
authors.forename: Kelly L
authors.initials: KL
authors.lastname: McCoy
authors.forename: S John
authors.initials: SJ
authors.lastname: Swanson
authors.forename: Roslyn B
authors.initials: RB
authors.lastname: Mannon
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D065095:Calcineurin Inhibitors; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab