Increased Frequency Of regulatory CD127low T Cells and of IL2+ T Cells Early after Lung Transplant is Associated with Improved Graft Survival

Purpose Regulatory T cells (Treg) may counteract chronic lung allograft dysfunction (CLAD). In the present study, we analyzed Treg in peripheral blood at 3 weeks and at 3, 6, 12 and 24 months after lung transplantation and correlated the percentages of 3 Treg subpopulations at 3 weeks with the later incidence of CLAD and graft survival. Methods Among lung-transplanted patients between January 2009 and October 2018, only adult patients with Treg measurements after transplantation were included into the study. Tregs were detected in peripheral blood and defined as CD4 + CD25 high T cells and further analyzed for CD127 low and FoxP3 + using FACS analysis. CD4 + CD25 high IL2 + T cells were also evaluated. Associations of Treg with CLAD and graft survival, defined as patient survival and freedom from re-transplantation, were evaluated using Cox analysis. Results Among the 1,089 lung-transplanted adult patients at our institution, 830 (76%) patients had Treg measurements after transplantation. Frequencies (%) of CD127 low and IL2 + but not of FoxP3 + cells were significantly higher in patients without CLAD than in patients with CLAD at each time point after transplantation (Figure 1). Similar results were found for graft survival. Treg frequencies were higher in patients treated with tacrolimus vs. cyclosporine. Follow-up was 42±29 months. Freedom (%) from CLAD was 66 at 5 years. At the Cox analysis, increasing frequencies of CD127 low (HR=0.988, p + Tregs (HR=0.989, p=0.016) but not of FoxP3 + (HR=0.991, p=0.11) were protective against CLAD. Graft survival (%) amounted to 68 at 5 years. Only increasing frequencies of CD127 low Tregs (HR=0.992, p=0.032) were protective against mortality or retransplantation. Conclusion A higher frequency of CD127 low Tregs early after lung transplantation is protective against CLAD and associated with better survival. The role of CD4 + CD25 high IL2 + T cells and the effect of tacrolimus on Treg deserve further investigation.