Involvement of indirectly allostimulated CD4 + CD43 high CD45RO + T cell proliferation in the development of chronic allograft nephropathy

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 241; no. 11; pp. 1217 - 1228
• Main Authors: Wee, Yu-Mee, Jung, Joo-Hee, Kim, Yang-Hee, Choi, Monica-Y, Kim, Young-Hoon, Choi, Do-Sook, Cho, Myung-Hwan, Han, Duck-Jong
• Format: Journal Article
• Language: English
• Published: 01.06.2016
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/1535370215601522

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.