Operational tolerance in the absence of immunosuppression can be successfully attained in pediatric liver transplant recipients. Although DSA are observed in a proportion of operationally tolerant (OT) recipients, they are not associated with rejection. We examined differences in T and B cell functions in liver recipients with stable allograft function in the absence of immunosuppression (OT) in comparison to those being weaned (WI), and maintained on immunosuppression (MI) (n=17–22/grp).

Methods: PBMC from OT, WI, and MI patients (>2yrs post transplant) were examined by 15-parameter FACS. T and B cell cytokine expression was tested after 24hr stimulation with CD3 and CpG DNA, respectively.

Results: (a) T cell analyses showed an increase in CD4 T_REG and a predominance of CD4 & CD8 effector memory in OT compared to WI or MI groups (n=8–11/grp, p<0.05). Memory T cells in OT were enriched in CD57+ cells expressing PD1 and 2B4 (indicative of replicative senescence). IL2 expression within the CD57+, CD4 & CD8 T cells was significantly attenuated in OT compared to others, while that in CD57- T cells was similar to others (n=6–10/grp, p<0.05). Also, in T cell culture supernatants, OT showed a significant decrease in secreted IFNg and CCL4 compared to MI (n=6–9/grp, p<0.05) suggesting functional exhaustion of T cells in OT recipients. (b) Class II DSA were found in all groups and were predominantly C1q binding in MI and WI but not OT (67%, 87%, 33%, respectively) while IgG4 was the major isotype in OT (63%) (n=17–22/grp). Memory B cells from OT expressed significantly less IL6 and IL12/23p40 cytokines compared to others (n=5–8/grp, p<0.05) suggesting that these B cells in OT subjects are poor stimulators.

Conclusions: Increased T_REG, functional T cell exhaustion, decreased B cell inflammatory cytokines and non-complement fixing DSA are the observed immune characteristics in operationally tolerant pediatric liver transplant recipients potentially contributing to allograft survival off immunosuppression.

CITATION INFORMATION: Ramaswami B., Marrari M., Yoshida O., Guo X., Hoffman W., Bentlejewski C., Metes D., Demetris A., Zeevi A., Thomson A., Mazariegos G., Chalasani G. T Cell Exhaustion Contributes to Operational Tolerance of Liver Allografts in Pediatric Liver Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress