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T Cell Exhaustion Contributes to Operational Tolerance of Liver Allografts in Pediatric Liver Transplant Recipients

B. Ramaswami,1 M. Marrari,2 O. Yoshida,5 X. Guo,3 W. Hoffman,3 C. Bentlejewski,2 D. Metes,1 A. Demetris,1,2 A. Zeevi,2 A. Thomson,1 G. Mazariegos,4 G. Chalasani.1,3

1Surgery, Starzl Transplantation Institute, Pittsburgh, PA
2Pathology, University of Pittsburgh, Pittsburgh, PA
3Medicine, University of Pittsburgh, Pittsburgh, PA
4Children's Hospital, University of Pittsburgh, Pittsburgh, PA
5Gastroenterology, Ehime University Graduate School of Medicine, Toon-shi, Ehime-ken, Japan.

Meeting: 2018 American Transplant Congress

Abstract number: 364

Keywords: B cells, Liver transplantation, Pediatric, T cells

Session Information

Date: Monday, June 4, 2018

Session Name: Concurrent Session: Liver: Pediatrics

Session Time: 4:30pm-6:00pm

 Presentation Time: 5:42pm-5:54pm

Location: Room 608/609

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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 TREG 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 TREG, 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).

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To cite this abstract in AMA style:

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 [abstract]. https://atcmeetingabstracts.com/abstract/t-cell-exhaustion-contributes-to-operational-tolerance-of-liver-allografts-in-pediatric-liver-transplant-recipients/. Accessed March 8, 2021.

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