Characterization of T cell immunophenotypes in intestinal transplantation: A pilot study

Abstract

Immunophenotyping of peripheral blood mononuclear cells has been shown to be a useful, non-invasive method of predicting acute cellular rejection (ACR) following intestinal transplantation (ITx). Our objectives were to characterize differences in the T cell immunophenotype of ITx recipients in peripheral blood samples (1) collected late versus early after ITx and (1) associated with episodes of ACR and infectious enteritis. An IRB-approved, cross-sectional study of ITx recipients was performed. Peripheral blood samples were collected during normal visits and episodes of allograft dysfunction. A total of 38 patients were included in the analysis: 31 ITx recipients (87% liver-inclusive allografts) and 7 intestinal failure control patients. Of the ITx patients, 26 patients were pediatric patients (<21 years). A total of 70 samples were analyzed from ITx recipients, including 51 during normal visits and 19 during episodes of allograft dysfunction (median of 2 samples per patient; range of 1-6 samples per patient). In the late (n = 32) versus early post-ITx (n = 19) normal samples, there was a significantly higher percentage of central memory CD4 T cells (p = .001). In the ACR (n = 5) versus infectious enteritis (n = 14) samples, there was a higher percentage of CD8 T cells expressing HLA-DR (p = .002), CD57 (p < .001), and KLRG1 (p < .001) and a higher percentage of CD4 T cells expressing CD57 (p = .03). Additional studies are needed with larger cohorts to validate these changes in the T cell immunophenotype. Further elucidating T cell immunophenotypes in ITx will lead to a better understanding of immune mechanisms of allograft dysfunction, identification of potential biomarkers in ITx, and optimized selection of immunosuppressive therapies.

T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients

“…In our study, CD57 and CD244 expression correlated positively with cytokine production in CD4 + T cells (and CD8 + T cells for CD57) from ABOi patients only. CD57 + CD4 + T cells have been associated with rejection in kidney‐grafted patients treated with belatacept , and CD57 + CD8 + T cells has been shown to be correlated with acute rejection upon intestinal transplantation . Conversely, low CD57 expression was associated with poor response to cytomegalovirus (CMV) infection .…”

Non‐HLA AT1R antibodies are highly prevalent after pediatric intestinal transplantation

“…All patients ≤18 years old followed by the UCLA Intestinal Transplant Program who received an ITx between 2000 and 2016 were eligible. All ITx recipients received an induction immunosuppression protocol consisting of corticosteroids and an interleukin‐2 receptor antagonist for 6–8 weeks post‐transplant in normal‐risk recipients, or rabbit anti‐thymocyte globulin or alemtuzumab in high‐risk recipients for induction therapy; and a maintenance regimen consisting of corticosteroids, tacrolimus, mycophenolate mofetil, and/or sirolimus 4,17 . Patients were included if AT1R antibody and HLA‐DSA testing were performed <100 days from one another.…”

“…This was a sub-study of our previously performed, prospective, cross-sectional study on the characterization of T-cell immunophenotypes associated with graft dysfunction after ITx, which showed an increase in markers of T-cell activation in graft rejection compared to infectious enteritis. 17 This current study retrospectively tested for the presence of AT1R antibodies in a subset of pediatric ITx recipients who had previously undergone HLA-DSA testing as part of routine clinical care. This study was approved by the UCLA Institutional Review Board, IRB #12-001231.…”