title: Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN-gamma+ blood lymphocytes in kidney transplant recipients with good long-term graft outcome.
abstract: There is evidence that interferon-gamma (IFN-gamma)-dependent interactions of dendritic cell (DC), T regulatory (Treg), and T suppressor (Ts) subpopulations contribute to allograft acceptance. We measured DC subsets, CD3+CD4+CD25+ (Treg phenotype) and CD3+CD8+CD28(-) (Ts phenotype) peripheral blood lymphocytes (PBL) expressing Foxp3, Th1 or Th2 cytokines, peripheral T- and B-cell counts, and plasma cytokines in 33 kidney transplant recipients with a serum creatinine of < or =1.8 mg/dl and 32 recipients with a serum creatinine of > or =2.0 mg/dl more than 100 days post-transplant. Cell subsets were measured in whole blood using four-color flow cytometry. Patients with increased creatinine had less frequently detectable CD3+CD4+CD25+IFN-gamma+ PBL than patients with good graft function (P = 0.017). In patients with good graft function, CD3+CD4+CD25+IFN-gamma+ PBL were associated with high Foxp3+, IL-2+, IL-12+, IL-4+, and IL-10+ CD3+CD4+CD25+ T PBL (P < 0.001), low CD3+CD8+CD28(-)Foxp3+ (P = 0.002), CD3+CD4+DR+ (P = 0.002), CD3+CD8+DR+ T (P = 0.005) and CD19+ B PBL (P = 0.005), and low lineage(-)HLA-DR+CD11c+CD123(-) DC1 (P = 0.006). Patients with impaired graft function did not show these associations. Additional flow cytometric analysis confirmed strong co-expression of IFN-gamma and Foxp3 by CD4+CD25+ PBL particularly in patients with good graft function. Our data support an immunoregulatory role of CD3+CD4+CD25+Foxp3+IFN-gamma+ cells in a subgroup of transplant recipients with good graft acceptance.
authors.affiliation: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany. volker.daniel@med.uni-heidelberg.de
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.forename: Cord
authors.initials: C
authors.lastname: Naujokat
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.forename: Fabrice
authors.initials: F
authors.lastname: Renner
authors.forename: Sevgi
authors.initials: S
authors.lastname: Yildiz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis*; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis* / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D016030:Kidney Transplantation / Q000502:physiology; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D019798:Neopterin; D007371:Interferon-gamma