Involvement of indirectly allostimulated CD4+CD43highCD45RO+ T cell proliferation in the development of chronic allograft nephropathy.
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.
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea Department of Biological Science, Konkuk University, Kwangjin-gu, Seoul 143-701, Korea.
Yu-Mee
YM
Wee
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea.
Joo-Hee
JH
Jung
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea.
Yang-Hee
YH
Kim
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea.
Monica-Y
MY
Choi
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea.
Young-Hoon
YH
Kim
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea.
Do-Sook
DS
Choi
Department of Biological Science, Konkuk University, Kwangjin-gu, Seoul 143-701, Korea mcho@konkuk.ac.kr.
Myung-Hwan
MH
Cho
Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Songpa-gu, Seoul 138-736, Korea djhan@amc.seoul.kr.
Duck-Jong
DJ
Han
D000328:Adult; D000368:Aged; D064591:Allografts; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D016030:Kidney Transplantation; D017493:Leukocyte Common Antigens / Q000032:analysis*; D051917:Leukosialin / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
D015415:Biomarkers; D016207:Cytokines; D051917:Leukosialin; C465014:SPN protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
CD4+CD43highCD45RO+ T cell; chronic allograft nephropathy; effector memory T cells; indirect allostimulation; induced protein-10; progression of acute rejection