title: Association of peripheral NK cell counts with Helios+IFN-γ-Tregsin patients with good long-term renal allograft function.
abstract: Little is known about a possible interaction of natural killer (NK) cells with regulatory T cells (Treg) in long-term stable kidney transplant recipients. Absolute counts of lymphocyte and Tregsubsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-colour fluorescence flow cytometry. Patients were 1946 ± 2201 days (153-10 268 days) post-transplant and showed a serum creatinine of 1·7 ± 0·7 mg/dl. Renal transplant recipients investigated > 1·5 years post-transplant showed higher total NK cell counts than recipients studied < 1·5 years after transplantation (P = 0·006). High NK cells were associated with high glomerular filtration rate (P = 0·002) and low serum creatinine (P = 0·005). Interestingly, high NK cells were associated with high CD4+CD25+CD127-forkhead box protein 3 (FoxP3+) Tregthat co-express the phenotype Helios+interferon (IFN)-γ-and appear to have stable FoxP3 expression and originate from the thymus. Furthermore, high total NK cells were associated with Tregthat co-express the phenotypes interleukin (IL)-10-transforming growth factor (TGF)-β+(P = 0·013), CD183+CD62L-(P = 0·003), CD183+CD62+(P = 0·001), CD183-CD62L+(P = 0·002), CD252-CD152+(P < 0·001), CD28+human leucocyte antigen D-related (HLA-DR-) (P = 0·002), CD28+HLA-DR+(P < 0·001), CD95+CD178-(P < 0·001) and CD279-CD152+(P < 0·001), suggesting that these activated Treghome in peripheral tissues and suppress effector cells via TGF-β and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). The higher numbers of NK and Tregcell counts in patients with long-term good allograft function and the statistical association of these two lymphocyte subsets with each other suggest a direct or indirect (via DC) interaction of these cell subpopulations that contributes to good long-term allograft acceptance. Moreover, we speculate that regulatory NK cells are formed late post-transplant that are able to inhibit graft-reactive effector cells.
authors.affiliation: Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Trojan
authors.affiliation: Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.|Department of Hematology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.|Nephrology Unit, Internal Medicine Department, Assiut University, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Aly
authors.affiliation: Department of Internal Medicine, University of Giessen, Giessen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Weimer
authors.affiliation: Department of Internal Medicine, University of Giessen, Giessen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Bulut
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Morath
authors.affiliation: Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Opelz
authors.affiliation: Transplantation-Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: V
authors.identifier: 0000-0001-8345-1031
authors.initials: V
authors.lastname: Daniel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D060908:CTLA-4 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D005919:Glomerular Filtration Rate; D006801:Humans; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000166:cytology*; D007958:Leukocyte Count; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D066027:Transplant Recipients; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D060908:CTLA-4 Antigen; D003404:Creatinine
keywords: CD8+ lymphocytes; CTLA-4; Helios+IFN-γ- Treg; TGF-β; Treg subsets; glomerular filtration rate; good long-term renal allograft function; peripheral NK cells; serum creatinine