Date: Tuesday, June 4, 2019
Session Name: Concurrent Session: Novel Insights in Kidney Infections
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: Room 311
*Purpose: Human herpesvirus (HHV)-6 reactivation after solid organ or hematopoietic stem cell transplant has been associated with complications such as graft rejection and all-cause mortality. Inadequate understanding of the interplay among viral replication, host immune response, and immunosuppression has limited progress toward better HHV6 management and outcomes. This study aims to 1) track the longitudinal kinetics of cellular reconstitution, HHV6-specific CD4 and CD8 T cell responses, and HHV6 DNAemia after induction immunosuppression with alemtuzumab or anti-thymocyte globulin in kidney transplant recipients, and 2) compare these parameters for HHV6 and cytomegalovirus (CMV), and for patients receiving each type of induction approach.
*Methods: Blood samples were collected prospectively from kidney transplant recipients before (< 3 mo) and after (monthly for 6 mo and at 12 mo) transplant. Samples from healthy adults were used as controls and to optimize assays. Flow cytometry is used to measure 1) lymphocyte (T and B cells) and non-lymphocyte (NK and dendritic cells and monocytes) populations ex vivo, and 2) CD4 or CD8 T cell responses (proliferation, cytokine production, cytotoxicity, and exhaustion) after stimulation with HHV6 or CMV whole virus lysates for 7 days. HHV6 and CMV DNA is measured in plasma by qPCR.
*Results: Studies for 15 patients at pre- and 2, 6, and 12 mo post-transplant, and data analysis on 10 of these patients, have been completed. HHV6- or CMV-specific T cell responses showed distinct features and kinetics over time. The following patterns have been observed: 1) Relatively few T cells were recovered or functional at 2 and 6 mo after transplant, 2) IFNg responses were not common, but detected more frequently than IL2 or TNFa, 3) CD4 T cells that mobilize CD107a/b and/or produce granzyme B were detected against both viruses, suggesting a cytolytic population, 4) T cells infrequently expressed PD1, perforin, IL2, or TNFa.
*Conclusions: In healthy immunocompetent adults and transplant recipients, HHV6-specific T cells are minimally detectable in PBMC ex vivo, but can be expanded in vitro for detailed characterization. CD4 and CD8 T cell responses evolve differentially over the first year, between related chronic viruses, and among individuals after kidney transplant. The role of induction immunosuppression regimen and/or viral reactivation on these patterns will be identified when data analysis is completed and blinding to these factors is removed.
To cite this abstract in AMA style:Gil A, Co M, Calvo-Calle M, Cruz J, Stern L, Gibson L. Evolution of HHV6- and CMV-Specific T Cell Functional Responses and Immune Cell Populations after Kidney Transplant [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/evolution-of-hhv6-and-cmv-specific-t-cell-functional-responses-and-immune-cell-populations-after-kidney-transplant/. Accessed April 15, 2021.
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