2017 - CIRTA

8- Immunological Monitoring, Rejection, and Mechanisms of Regeneration

36.10 - Immune memory after intestinal transplantation – what can we learn from T cell immunophenotypes over time?

Presenter: Marjorie-Anne, Guerra, Los Angeles, United States
Authors: Marjorie-Anne Guerra, Maura Rossetti, Robert Venick, Elizabeth Marcus, Suzanne McDiarmid, Elaine Cheng, Douglas Farmer, Elaine Reed, Laura Wozniak

Immune memory after intestinal transplantation – what can we learn from T cell immunophenotypes over time?

Marjorie-Anne R. Guerra1, Maura Rossetti2, Robert S. Venick1,3, Elizabeth A. Marcus1, Suzanne V. McDiarmid1,3, Elaine Y. Cheng3, Douglas G. Farmer3, Elaine F. Reed2, Laura J. Wozniak1.

1Pediatric Gastroenterology, Hepatology, and Nutrition, UCLA, Los Angeles, CA, United States; 2Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, United States; 3Transplant Surgery, UCLA, Los Angeles, CA, United States

Introduction: Examination of peripheral blood mononuclear cells (PBMCs) via immunophenotyping has been shown to be a useful, non-invasive method of diagnosing acute cellular rejection (ACR) following intestinal transplantation (ITx)[1]. Aims: To characterize (1) differences in the peripheral blood T cell immunophenotype during episodes of ACR and viral enteritis and (2) changes in naïve and central/effector memory T cells over time.

Methods: An IRB-approved, longitudinal study of ITx recipients was performed. Blood was collected during serial routine visits at least 6 months apart and episodes of graft dysfunction (high fecal outputs, nausea/vomiting, and/or gastrointestinal bleeding). Samples from routine visits were classified as early post-ITx (<5 yrs) and late post-ITx (>5 yrs). PBMC immunophenotyping was performed with multi-color monoclonal antibody panels. Cell fluorescence was acquired on an LSR Fortessa. Analysis was performed with Flowjo V10. Statistical analyses included t-tests using Stata.

Results: 11 pediatric ITx recipients who received 14 grafts were included. 57% were liver-intestinal grafts. 28 samples were analyzed (range of 1-5 samples per patient): 20 were collected on routine visits and 8 during episodes of graft dysfunction. There were no significant differences in markers of exhaustion (PD1+, KLRG1+, CD57+), Th17 effector cells, or T regulatory cells in normal (n=11) vs graft dysfunction (n=8). There were multiple statistically significant differences in T cell subsets in the early (n=7) vs late (n=13) groups (Table 1). Naïve T cells were higher in the early post-ITx group and T central memory cells were higher in the late post-ITx group.

Conclusion: Over time, there is a shift in the T cell immunophenotype from naïve to central memory cells. Additional studies are needed with larger cohorts to identify T cell differences associated with episodes of graft dysfunction. Further elucidating T cell immunophenotypes over time will lead to a better understanding of immune memory and its clinical implications in ITx.

[1] Ashokkumar C et al. Allospecific CD154+ T cells identify rejection-prone recipients after pediatric small-bowel transplantation. Surgery. 2009; 146:166-73.

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