The role of age-related T-cell differentiation in patients with renal replacement therapy

被引:12
作者
Schaier, Matthias [1 ]
Leick, Angele [2 ]
Uhlmann, Lorenz [3 ]
Kaelble, Florian [1 ]
Eckstein, Volker [4 ]
Ho, Anthony [4 ]
Meuer, Stefan [5 ]
Mahnke, Karsten [6 ]
Sommerer, Claudia [1 ]
Zeier, Martin [1 ]
Steinborn, Andrea [2 ]
机构
[1] Heidelberg Univ, Dept Med Nephrol 1, Heidelberg, Germany
[2] Heidelberg Univ, Dept Obstet & Gynecol, INF 440, D-69120 Heidelberg, Germany
[3] Heidelberg Univ, Inst Med Biometry & Informat, Heidelberg, Germany
[4] Heidelberg Univ, Dept Med Hematol 5, Heidelberg, Germany
[5] Heidelberg Univ, Inst Immunol, Heidelberg, Germany
[6] Heidelberg Univ, Dept Dermatol, Heidelberg, Germany
关键词
KIDNEY-TRANSPLANTATION; HEMODIALYSIS-PATIENTS; DISEASE PATIENTS; ESRD PATIENTS; EXPRESSION; INFLAMMATION; LYMPHOCYTES; DYSFUNCTION; INFECTION; PREGNANCY;
D O I
10.1038/icb.2017.57
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Dialysis patients have deficiencies regarding the generation of immune responses and show an increased susceptibility for infections. Persisting uremic conditions are made responsible for the increased aging of their immune system. In this study, we analyzed whether age-related differences in the differentiation of both recent-thymic-emigrant-(RTE)-regulatory (Tregs) and RTE-responder T cells (Tresps) into CD31(-)-memory Tregs/Tresps led to differences in the suppressive activity of naive and memory Tregs on autologous Tresps between healthy volunteers and dialysis patients. We found that regardless of age, the differentiation of RTE-Treg/Tresps into CD31(-)-memory-Treg/Tresps was significantly increased in dialysis patients. By analyzing the age-related differences in the differentiation of Tregs/Tresps, we saw that in healthy volunteers RTE-Tregs differentiate via CD31(+)-memory Tregs into CD31(-)-memory Tregs, which may strengthen the suppressive activity of the total Treg pool. In contrast RTE-Tresps of healthy volunteers differentiate via mature naive (MN)-Tresps into CD31(-)-memory-Tresps, which may weaken the reactivity of the total Tresp pool. Our data revealed that this normal differentiation via MN-Tresps was lost in dialysis patients, suggesting that their Tresps are less sensitive to Treg-mediated immunosuppression. Functional analysis of Tregs on autologous Tresps showed an increasing suppressive activity with age in healthy individuals, who therefore may have a lower risk of developing autoimmune diseases but owing to decreased reactivity of their Tresps are more likely to suffer from infections. In contrast, dialysis patients exhibited a decreasing suppressive activity with age, owing to strengthened Tresp reactivity, which could explain the higher prevalence of chronic inflammatory conditions in these patients.
引用
收藏
页码:895 / 905
页数:11
相关论文
共 36 条
[1]   Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls: Implications for Cell Therapy in Transplantation [J].
Afzali, Behdad ;
Edozie, Francis C. ;
Fazekasova, Henrieta ;
Scotta, Cristiano ;
Mitchell, Peter J. ;
Canavan, James B. ;
Kordasti, Shahram Y. ;
Chana, Prabhjoat S. ;
Ellis, Richard ;
Lord, Graham M. ;
John, Susan ;
Hilton, Rachel ;
Lechler, Robert I. ;
Lombardi, Giovanna .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 8 (08) :1396-1405
[2]   Isolation, expansion and functional assessment of CD4+CD25+FoxP3+regulatory T cells and Tr1 cells from uremic patients awaiting kidney transplantation [J].
Berglund, David ;
Korsgren, Olle ;
Lorant, Tomas ;
Schneider, Karin ;
Tufveson, Gunnar ;
Carlsson, Bjorn .
TRANSPLANT IMMUNOLOGY, 2012, 26 (01) :27-33
[3]   Chronic Kidney Disease and Premature Ageing of the Adaptive Immune Response [J].
Betjes, Michiel G. H. ;
Litjens, Nicolle H. R. .
CURRENT UROLOGY REPORTS, 2014, 16 (01) :1-7
[4]   Immune cell dysfunction and inflammation in end-stage renal disease [J].
Betjes, Michiel G. H. .
NATURE REVIEWS NEPHROLOGY, 2013, 9 (05) :255-265
[5]   A killer on the road: circulating CD4+CD28null T cells as cardiovascular risk factor in ESRD patients [J].
Betjes, Michiel G. H. ;
Meijers, Ruud W. J. ;
de Wit, Lucia E. A. ;
Litjens, Nicolle H. R. .
JOURNAL OF NEPHROLOGY, 2012, 25 (02) :183-191
[6]   Premature aging of circulating T cells in patients with end-stage renal disease [J].
Betjes, Michiel G. H. ;
Langerak, Anton W. ;
van der Spek, Ashley ;
de Wit, Elly A. ;
Litjens, Nicolle H. R. .
KIDNEY INTERNATIONAL, 2011, 80 (02) :209-218
[7]   Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients [J].
Betjes, Michiel G. H. ;
de Wit, Elly E. A. ;
Weimar, Willem ;
Litjens, Nicolle H. R. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (11) :3640-3646
[8]   Regulatory T-cells at the interface between human host and pathogens in infectious diseases and vaccination [J].
Boer, Mardi C. ;
Joosten, Simone A. ;
Ottenhoff, Tom H. M. .
FRONTIERS IN IMMUNOLOGY, 2015, 6
[9]   Sex, the aging immune system, and chronic disease [J].
Bupp, Melanie R. Gubbels .
CELLULAR IMMUNOLOGY, 2015, 294 (02) :102-110
[10]   Neutrophil dysfunction and infection risk in end-stage renal disease [J].
Chonchol, Michel .
SEMINARS IN DIALYSIS, 2006, 19 (04) :291-296