A. As the pathophysiologic role of Tissue Resident Memory T Cells (T_RM) in intestinal transplantation (ITx) is unknown, this study aims to test the hypothesis that T_RM play a critical effector role in graft-versus-host disease (GvHD) in ITx patients.

B. A cohort of 16 recent ITx patients was prospectively immunomonitored via serial blood and allograft polychromatic flow cytometry (PFC) starting one day before ITx. Five patients with clinically and pathologically confirmed GvHD were identified with onsets between (40-59, mean=46) days after ITx. CD3⁺ T_RM cells were phenotypically defined as CD62L^–CD45RO^+/-CD69⁺CD103^+/-, effector memory T cells (T_EM) as CD45RO⁺CD62L^– or CCR7^–CD45RA^–.

C. Importantly, immunomonitoring results revealed significantly higher frequencies of allograft CD8⁺ T_RM (68.2%) with an effector memory phenotype in the GvHD group versus the stable ITx cohort (23.9%)(p=0.0065) at the time of GvHD diagnosis. This was accompanied by a trend towards lower mean frequencies of allograft CD4⁺ T_RM in GvHD versus stable ITx patients (12.7% vs. 31.0%, p>0.05). Moreover, immunophenotyping of pre-reperfusion backtable samples confirmed the predominance of donor effector memory type CD8⁺ T_RM (81.3%) in the allografts of GvHD patients prior to ITx. Thus, allograft-derived CD8⁺ T_RM may be critical effector cells which, after engraftment and recirculation, initiate the process of GvHD. This hypothesis was corroborated by serial blood immunomonitoring which demonstrated an increase in CD8⁺ T_EM immediately prior to presentation of GvHD (56%) versus pre-GvHD baseline (26%).

D. Prospective immunomonitoring indicates that donor allograft derived effector memory type CD8⁺ T_RM may re-circulate after ITx and operate as effectors of GvHD, which may have important diagnostic and therapeutic implications.

CITATION INFORMATION: Aguirre O., Houlihan B., Karabala A., Girlanda R., Hawksworth J., Matsumoto C., Zasloff M., Fishbein T., Kroemer A. CD8⁺ Tissue Resident Memory T Cells Are Key Effector Cells in Intestinal Transplantation Patients with GvHD Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress