title: Increased levels of CD4(+) and CD8(+) T cells expressing CCR1 in patients developing allograft dysfunction; a cohort study.
abstract: Leukocyte infiltration into the graft has pivotal effects on kidney transplantation outcome. The present study sought to determine whether the expression of sequential chemokine receptors on CD4(+) and CD8(+) T cells in human renal allograft can predict clinical episodes.
  
  
  
  Blood samples from 52 consecutive renal transplant patients were evaluated at the time of transplantation and at three times (2, 90 and 180days) after transplantation to analyze the expression of CCR1 and CXCR3 on CD4(+) and CD8(+) T cells by flowcytometry. A total of 30 biopsies, including protocol biopsy (n=24) and cause biopsy (n=6), were investigated according to the Banff criteria.
  
  
  
  The mean percentage of CD4(+) and CD8(+) T cells expressing CCR1 was significantly increased in patients with allograft dysfunction (n=25) (p=0.006, p=0.004). The mean fluorescence intensity of CXCR3 on CD4(+) and CD8(+) T cells were found to be significantly higher in graft dysfunction than that in well-functioning grafts. (p<0.001, p=0.007). Receiver Operating Characteristic (ROC) Curve Analysis showed that the calculated AUC was 0.86 at the third month for CD4(+)CCR1(+) and CD8(+)CCR1(+) (p<0.001). Multiple logistic regression analysis showed that an increase in CD4(+) expressing CXCR3 leads to a lower risk of graft dysfunction (OR=0.37), while an increase in CD8(+) expressing CCR1 results in a higher risk of graft dysfunction (OR=3.66).
  
  
  
  During renal transplantation, CD4(+) and CD8(+) T cells expressing CCR1 were increased in patients who developed graft dysfunction. These findings may prospectively predict allograft dysfunction, and help elucidate the underlying pathogenic mechanisms.
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farshad
authors.initials: F
authors.lastname: Foroughi
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: amirzara@sina.tums.ac.ir.
authors.forename: Aliakbar
authors.initials: A
authors.lastname: Amirzargar
authors.affiliation: Chronic Kidney Disease Research Center, Department of Nephrology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Pedram
authors.initials: P
authors.lastname: Ahmadpoor
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farshid
authors.initials: F
authors.lastname: Noorbakhsh
authors.affiliation: Chronic Kidney Disease Research Center, Department of Nephrology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nafar
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mir Saeed
authors.initials: MS
authors.lastname: Yekaninejad
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Hosseinzadeh
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sanaz Keshavarz
authors.initials: SK
authors.lastname: Shabaz
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Barabadi
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Ghorbanpour
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: saraf@sphtums.com.
authors.forename: Abdolfattah
authors.initials: A
authors.lastname: Sarrafnejad
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D015331:Cohort Studies; D051799:Delayed Graft Function / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D054389:Receptors, CCR1 / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000378:metabolism*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C515300:CCR1 protein, human; C515187:CXCR3 protein, human; D054389:Receptors, CCR1; D054367:Receptors, CXCR3
keywords: Acute rejection; Chemokine receptor; Graft dysfunction; Renal transplantation