Donor-Reactive Regulatory T Cell Frequency Increases During Acute Cellular Rejection of Lung Allografts. Issue 10 (October 2016)

• Record Type: Journal Article
• Authors: Greenland, John R.; Wong, Charissa M.; Ahuja, Rahul; Wang, Angelia S.; Uchida, Chiyo; Golden, Jeffrey A.; Hays, Steven R.; Leard, Lorriana E.; Rajalingam, Raja; Singer, Jonathan P.; Kukreja, Jasleen; Wolters, Paul J.; Caughey, George H.; Tang, Qizhi
• Is Part Of: Transplantation. Volume 100:Issue 10(2016)
• Publication Date: 2016-10
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001191
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: Acute cellular rejection is a major cause of morbidity after lung transplantation. Because regulatory T (Treg) cells limit rejection of solid organs, we hypothesized that donor-reactive Treg increase after transplantation with development of partial tolerance and decrease relative to conventional CD4 + (Tconv) and CD8 + T cells during acute cellular rejection. Methods: To test these hypotheses, we prospectively collected 177 peripheral blood mononuclear cell specimens from 39 lung transplant recipients at the time of transplantation and during bronchoscopic assessments for acute cellular rejection. We quantified the proportion of Treg, CD4 + Tconv, and CD8 + T cells proliferating in response to donor-derived, stimulated B cells. We used generalized estimating equation-adjusted regression to compare donor-reactive T cell frequencies with acute cellular rejection pathology. Results: An average of 16.5 ± 9.0% of pretransplantation peripheral blood mononuclear cell Treg cell were donor-reactive, compared with 3.8% ± 2.9% of CD4 + Tconv and 3.4 ± 2.6% of CD8 + T cells. These values were largely unchanged after transplantation. Donor-reactive CD4 + Tconv and CD8 + T cell frequencies both increased 1.5-fold (95% confidence interval [95% CI], 1.3-1.6; P < 0.001 and 95% CI, 1.2-1.6; P = 0.007, respectively) during grade A2 rejection compared with no rejection. Surprisingly, donor-reactive Treg frequencies increased by 1.7-fold (95% CI, 1.4-1.8; P < 0.001). Conclusions: Contrary to prediction, overall proportions of donor-reactive Treg cells are similar before and after transplantation and increase during grade A2 rejection. This suggests how A2 rejection can be self-limiting. The observed increases over high baseline proportions in donor-reactive Treg were insufficient to prevent acute lung allograft rejection. Abstract : A balance between Treg and nonregulatory T cells may determine allograft survival or rejection. Analysis of donor-reactive CD4+ Treg aswell as CD4+ andCD8+ conventional T cells in lung transplanted patients show that contrary to prediction, during acute rejection not only nonregulatory CD4+ and CD8+ cells but also CD4+ Treg increase. Supplemental digital content is available in the text.