title: Association of Higher CD4+CD25highCD127low, FoxP3+, and IL-2+T Cell Frequencies Early After Lung Transplantation With Less Chronic Lung Allograft Dysfunction at Two Years.
abstract: Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung-transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12, and 24 months after transplantation and were defined as CD4+CD25highT cells and further analyzed for CTLA4, CD127, FoxP3, and IL-2 expressions. Between January 2009 and July 2011, 264 patients were transplanted at our institution. Among the 138 (52%) patients included into the study, 31 (22%) developed CLAD within 2 years after transplantation. As soon as 3 weeks after lung transplantation, a statistically significant positive association was detected between Treg frequencies and later absence of CLAD. At the multivariate analysis, increasing frequencies of CD4+CD25highCD127low, CD4+CD25highFoxP3+and CD4+CD25highIL-2+T cells at 3 weeks after lung transplantation emerged as protective factors against development of CLAD at 2 years. In conclusion, higher frequencies of specific Treg subpopulations early after lung transplantation are protective against CLAD development.
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Salman
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ius
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: A-K
authors.initials: AK
authors.lastname: Knoefel
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Sommer
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Siemeni
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kuehn
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Tudorache
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Avsar
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Nakagiri
authors.affiliation: Department of Surgery, Munich Lung Transplant Group, Ludwig-Maximilian's University, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Preissler
authors.affiliation: Department of Surgery, Munich Lung Transplant Group, Ludwig-Maximilian's University, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hatz
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Greer
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.affiliation: Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Warnecke
mesh_terms: D064591:Allografts; D015415:Biomarkers / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008171:Lung Diseases / Q000601:surgery*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508594:IL2 protein, human; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit
keywords: T cell biology; clinical research/practice; lung (allograft) function/dysfunction; lung transplantation/pulmonology