title: A higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.
abstract: Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RC(high) T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients' CD8 T cells.
authors.affiliation: Inserm, U1043, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ordonez
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bernard
authors.forename: Marianne
authors.initials: M
authors.lastname: Chabod
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Augusto
authors.forename: Valerie
authors.initials: V
authors.lastname: Lauwers-Cances
authors.forename: Christelle
authors.initials: C
authors.lastname: Cristini
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Cuturi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Subra
authors.forename: Abdelhadi
authors.initials: A
authors.lastname: Saoudi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies
chemical_list: D017493:Leukocyte Common Antigens
references.citation: J Exp Med. 1994 Feb 1;179(2):589-600
references.pmid: 7905019
references.citation: J Exp Med. 1987 Nov 1;166(5):1548-66
references.pmid: 2824653
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4793-8
references.pmid: 19273860
references.citation: Blood. 2007 Apr 1;109(7):3115-23
references.pmid: 17148592
references.citation: Blood. 2004 Oct 15;104(8):2403-9
references.pmid: 15231569
references.citation: Immunol Rev. 1996 Feb;149:195-216
references.pmid: 9005215
references.citation: Immunol Rev. 1991 Oct;123:37-64
references.pmid: 1684782
references.citation: Annu Rev Immunol. 2003;21:107-37
references.pmid: 12414720
references.citation: Annu Rev Immunol. 2004;22:745-63
references.pmid: 15032595
references.citation: J Exp Med. 1990 Dec 1;172(6):1701-8
references.pmid: 2258700
references.citation: Nat Immunol. 2009 Jun;10(6):603-9
references.pmid: 19448631
references.citation: Blood. 2008 Sep 1;112(5):2101-10
references.pmid: 18596226
references.citation: Annu Rev Immunol. 2012;30:531-64
references.pmid: 22224781
references.citation: Nat Rev Immunol. 2012 May 25;12(6):417-30
references.pmid: 22627860
references.citation: J Clin Invest. 2003 Jun;111(12):1887-95
references.pmid: 12813024
references.citation: Transplantation. 2009 May 15;87(9 Suppl):S69-74
references.pmid: 19424013
references.citation: J Exp Med. 1994 Feb 1;179(2):493-502
references.pmid: 7905018
references.citation: J Exp Med. 1983 Sep 1;158(3):795-810
references.pmid: 6224884
references.citation: J Immunol. 2004 Sep 1;173(5):3140-7
references.pmid: 15322174
references.citation: Nature. 1996 Apr 25;380(6576):717-20
references.pmid: 8614467
references.citation: J Clin Invest. 2010 Jun;120(6):1836-47
references.pmid: 20501946
references.citation: Transplantation. 2006 Sep 27;82(6):844-8
references.pmid: 17006334
references.citation: Immunol Rev. 2001 Dec;184:145-60
references.pmid: 12086309
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: Immunol Rev. 2013 Mar;252(1):183-91
references.pmid: 23405905
references.citation: J Exp Med. 2006 Nov 27;203(12):2715-25
references.pmid: 17101734
references.citation: N Engl J Med. 2005 Mar 31;352(13):1371-3
references.pmid: 15800234
references.citation: N Engl J Med. 2000 Mar 2;342(9):605-12
references.pmid: 10699159
references.citation: J Immunol. 1999 Nov 15;163(10):5353-7
references.pmid: 10553059
references.citation: Nat Rev Immunol. 2011 Feb;11(2):119-30
references.pmid: 21267013
references.citation: J Immunol. 2001 Mar 15;166(6):3789-96
references.pmid: 11238621
references.citation: Nat Immunol. 2001 May;2(5):389-96
references.pmid: 11323691
references.citation: Annu Rev Pathol. 2008;3:189-220
references.pmid: 18039144
references.citation: Annu Rev Immunol. 1989;7:339-69
references.pmid: 2523715
references.citation: PLoS One. 2009;4(4):e5287
references.pmid: 19381293
references.citation: Eur J Immunol. 2004 Feb;34(2):408-17
references.pmid: 14768045
references.citation: J Mol Med (Berl). 1998 Jul;76(8):572-80
references.pmid: 9694434
references.citation: J Immunol. 2001 Mar 1;166(5):2944-52
references.pmid: 11207243
references.citation: Trends Immunol. 2006 Mar;27(3):146-53
references.pmid: 16423560
references.citation: Nature. 1990 Aug 30;346(6287):844-7
references.pmid: 2118234
references.citation: J Clin Invest. 2007 Apr;117(4):1096-106
references.pmid: 17404623
references.citation: J Clin Invest. 2010 Jun;120(6):1848-61
references.pmid: 20501943
references.citation: Blood. 2004 Nov 15;104(10):3294-301
references.pmid: 15271801
references.citation: Genes Immun. 2013 Jun;14(4):258-67
references.pmid: 23615071
references.citation: N Engl J Med. 1990 Feb 22;322(8):510-7
references.pmid: 2405272
references.citation: J Immunol. 2002 Feb 1;168(3):1080-6
references.pmid: 11801641
references.citation: J Clin Invest. 2003 Jul;112(1):101-8
references.pmid: 12840064
references.citation: Blood. 2009 Apr 30;113(18):4240-9
references.pmid: 19171879
references.citation: Blood. 2008 Feb 15;111(4):2476-84
references.pmid: 18045967
references.citation: Transplant Rev (Orlando). 2009 Jan;23(1):11-8
references.pmid: 19027613
references.citation: Immunol Rev. 2003 Dec;196:65-74
references.pmid: 14617198
references.citation: J Immunol. 1990 Jun 15;144(12):4648-50
references.pmid: 2112572
references.citation: Nat Med. 2005 Jun;11(6):605-13
references.pmid: 15937473