Cytomegalovirus-specific T cells restricted for shared and donor human leukocyte antigens differentially impact on cytomegalovirus reactivation risk after allogeneic hematopoietic stem cell transplantation

Abstract

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the emergence of circulating Cytomegalovirus(CMV)-specific T cells correlates with protection from CMV reactivation, an important risk factor for non-relapse mortality. However, functional assays measuring CMV-specific cells are time-consuming and often inaccurate at early timepoints. We report results of a prospective single-center non-interventional study which identifies the enumeration of Dextramer-positive CMV-specific lymphocytes as a reliable and early predictor of viral reactivation. We longitudinally monitored 75 consecutive patients for 1 year after allo-HSCT (n=630 samples). The presence of ≥0.5 CMV-specific CD8+ cells//L at day+45 was an independent protective factor from subsequent clinicallyrelevant reactivation in univariate(p

Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant

“…This would be expected to affect responses, especially if effective clearance by T cells specific for certain epitopes depends upon attainment and/or maintenance of critical levels of these T cells both in sites of infection and the circulation. A recent prospective study ( 41 ) employed dextramers binding CMV epitopes complexed with their presenting HLA alleles to quantitate reconstitution of CMV-specific T cells and identified levels of over 0.5 CMV-specific CD8 + T cells/μL by day 45 after transplant as protective from clinically relevant CMV reactivation. Our cohort was too small to identify a range of CMV-specific T cell levels associated with clearance of CMV viremia.…”

Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia

“…This observation probably resulted from both the in-vivo T-cell depletion with PT-Cy and the reasonably fast viral clearance achieved at day +28 after transplant, thus limiting antigen exposure and the subsequent development of SARS-CoV-2-specific response despite good functional T-cell recovery observed for polyclonal stimuli. In the early phase after PT-Cy-based transplants, the rate of viral infections is high and the emergence of viral-specific T-cells in primary immunological responses has been shown to be largely sustained by antigen encounter on host-infected cells rather than by cross-priming/presentation by non-infected donor-derived antigen-presenting cells ( 26 , 27 ).…”

Slaying the “Troll of Transplantation”—new frontiers in cytomegalovirus management: A report from the CMV International Symposium 2023

“…In major histocompatibility (MHC)‐multimer‐based assays, peptide‐specific T cells are stained using peptide‐conjugated MHC class 1 tetramers or pentamers to determine CD8+ T‐cell responses 57 . These strategies may also allow comparative analysis of lymphocytes restricted by shared, donor‐ and host‐specific HLA to track thymic‐independent CMV‐specific reconstitution 58 . However, this method requires knowledge of HLA type and, like intracellular staining, needs fluorescence‐activated cell sorting facilities.…”