title: Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies.
abstract: T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1 year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1 year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12 months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3 months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1 year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7-) were observed from baseline up to more than 1 year after transplantation. Rejection was associated with higher levels of these cells during the first 6 months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.
authors.affiliation: Transplant Immunology Group, Clinical Immunology Department, University Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Lanio
authors.forename: E
authors.initials: E
authors.lastname: Sarmiento
authors.forename: A
authors.initials: A
authors.lastname: Gallego
authors.forename: J
authors.initials: J
authors.lastname: Navarro
authors.forename: J
authors.initials: J
authors.lastname: Palomo
authors.forename: J
authors.initials: J
authors.lastname: Fernandez-Yañez
authors.forename: M
authors.initials: M
authors.lastname: Ruiz
authors.forename: E
authors.initials: E
authors.lastname: Fernandez-Cruz
authors.forename: J
authors.initials: J
authors.lastname: Carbone
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D000077561:Daclizumab; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D000077561:Daclizumab
keywords: Flow cytometry; Heart transplantation; Immune monitoring; Kinetics; Lymphocyte subset