Involvement of indirectly allostimulated CD4+CD43highCD45RO+ T cell proliferation in the development of chronic allograft nephropathy

Exp Biol Med (Maywood). 2016 Jun;241(11):1217-28. doi: 10.1177/1535370215601522. Epub 2015 Sep 7.

Abstract

The goal of this study was to identify immunological markers for use in antigen-specific assays that predict long-term survival after renal allograft and distinguish stable-functioning (SP) patients from poorly functioning (PP) patients. For this prospective study, 20 patients were enrolled. Eight SP and six PP patients were enrolled in this study. Serum cytokine/chemokine levels were analyzed by the Luminex multiplex assay. To detect indirect alloreactive T cells, we performed indirect mixed lymphocyte reaction using donor-antigen-pulsed autologous dendritic cells as stimulators. Serum induced protein-10 levels were significantly higher in the serum of PP patients, whereas sCD40L levels were higher in SP patients. The PP patients had significantly higher numbers of donor-specific CD4(+)CD43(high)CD45RO(+) T cells after indirect allostimulation, whereas this cell population was unchanged in SP patients. The donor-specific CD4(+)CD43(high)CD45RO(+) T cells had the effector memory T cell phenotype. Prospectively, we studied whether these cells influence graft outcome and found that their strong proliferation in pre-transplant patients is related to a poorly functioning graft. Indirectly allostimulated CD4(+)CD43(high)CD45RO(+) T cells may not only contribute to chronic allograft nephropathy development but may also have a role in the progression of acute rejection. Thus, these cells may have potential use as immune-monitoring markers in a noninvasive in vitro assay that predicts graft outcome.

Keywords: CD4+CD43highCD45RO+ T cell; chronic allograft nephropathy; effector memory T cells; indirect allostimulation; induced protein-10; progression of acute rejection.

MeSH terms

  • Adult
  • Aged
  • Allografts*
  • Biomarkers / analysis
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / blood
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / pathology*
  • Humans
  • Kidney Transplantation*
  • Leukocyte Common Antigens / analysis*
  • Leukosialin / analysis*
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / immunology*

Substances

  • Biomarkers
  • Cytokines
  • Leukosialin
  • SPN protein, human
  • Leukocyte Common Antigens
  • PTPRC protein, human