Reconstitution of T-Cell Subsets Following Thymoglobulin-Induced Depletion in High Immunologic Risk and Donation After Cardiac Death Renal Transplant Recipients

Masoud Akbari; Manujendra N Saha; Siobhan Telfer; Sha Ullah; Amy Mok; Vivian McAlister; Smriti Juriasingani; Patrick P Luke; Alp Sener

doi:10.1016/j.transproceed.2019.03.024

Reconstitution of T-Cell Subsets Following Thymoglobulin-Induced Depletion in High Immunologic Risk and Donation After Cardiac Death Renal Transplant Recipients

Transplant Proc. 2019 Jul-Aug;51(6):1744-1753. doi: 10.1016/j.transproceed.2019.03.024.

Authors

Masoud Akbari¹, Manujendra N Saha¹, Siobhan Telfer², Sha Ullah³, Amy Mok⁴, Vivian McAlister², Smriti Juriasingani⁴, Patrick P Luke⁵, Alp Sener⁶

Affiliations

¹ Department of Surgery, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, Western University, London, Ontario, Canada.
² Department of Surgery, Western University, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
³ Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
⁴ Department of Microbiology & Immunology, Western University, London, Ontario, Canada.
⁵ Department of Surgery, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, Western University, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
⁶ Department of Surgery, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, Western University, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada; Department of Microbiology & Immunology, Western University, London, Ontario, Canada. Electronic address: alp.sener@lhsc.on.ca.

PMID: 31399162
DOI: 10.1016/j.transproceed.2019.03.024

Abstract

Introduction: Depletion therapy in high immunologic risk (HR) patients by antithymocyte globulin (rATG) induces lymphopenia and subsequent compartmental repopulation of T-cell subsets. rATG is also given to patients receiving kidneys from donations after cardiac death (DCDs) to mitigate innate immune activation associated with the DCD process.

Methods: We compared the T-cell response with rATG in both HR and DCD kidney recipients. We examined the reconstitution of T-cell subsets after rATG treatment in HR and DCD recipients (n = 19 per group) by multicolor flow cytometry.

Results: Following treatment, there was a rapid drop in the frequency of T cells in both groups, which persisted over 28 days. HR patients had an early surge in the frequency of CD4⁺ naïve, effector-memory, and regulatory T cells. Although we found a significant proliferation of the T cells in both groups, the DCD cohort had a blunted response as well as reduced CD4⁺ T-cell immune-reactivity compare with the HR group.

Conclusions: Our data suggest that there is a lack of significant homeostatic proliferative response in DCD recipients following rATG, and CD4⁺ T cells may be less reactive in the DCD group than previously thought, indicating that rATG treatment may not have to be considered a first-line induction therapy in DCD recipients.

MeSH terms

Antilymphocyte Serum / therapeutic use*
Female
Graft Rejection / immunology
Graft Rejection / prevention & control
Humans
Immunosuppressive Agents / therapeutic use*
Kidney Transplantation / methods*
Male
Middle Aged
Risk Factors
T-Lymphocyte Subsets / drug effects*
Tissue Donors

Substances

Antilymphocyte Serum
Immunosuppressive Agents