Expansion of Phenotypically Senescent CD57+ CD8 T Cells Is Associated with Impaired Immunocompetence after Allogeneic Hematopoietic Stem Cell Transplantation

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1807-1807
• Main Authors: Morin, Sarah, Pradier, Amandine, Giannotti, Federica, Mamez, Anne-Claire, Vu-Cantero, Diem-Lan, Fabra-Urdiola, Marta, Stephan, Caroline, Bernardi, Chiara, Melotti, Astrid, Masouridi-Levrat, Stavroula, Roosnek, Eddy, Kaiser, Laurent, Chalandon, Yves, Simonetta, Federico
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-153133

Background: T cell senescence is a physiological process typically associated with aging. In addition, lymphopenia and chronic immune activation can result in T cell senescence. CD57, a member of the N-CAM family initially described as a natural killer cell marker, has been reported as a marker of human senescent CD8 T cells. Percentages of CD57+ CD8 T cells increase during aging as well as during chronic viral infections. Early studies have reported increased proportions of CD57-expressing CD8 T cells after autologous and allogeneic hematopoietic stem cell transplantation (HSCT). Whether these cells can be considered a counterpart of the senescent population found during aging is at present unknown. More importantly, whether the expansion of CD57+ CD8 T cells is associated with impaired immunocompetence after allogeneic HSCT remains to be investigated. Materials and Methods: With written informed consent, peripheral blood mononuclear cells were collected from healthy controls (HC, n=21) and patients undergoing allogeneic HSCT (n=115) at Geneva University Hospitals. Proportions of CD57+ CD8 T cells as well as phenotypic and functional characteristics of CD57+ CD8 T cells were assessed by flow cytometry. Virus-specific CD8 T cells were identified by flow cytometry based on IFNg and/or TNFa intra-cytoplasmic expression after 6h in vitro stimulation with peptides derived from CMV, EBV, HHV6, BKV and Adenovirus. Torque Teno Virus (TTV) replication was quantified by quantitative PCR as previously described (Pradier et al., Front Immunol 2020; doi: 10.3389/fimmu.2020.00998). Results: CD8 T cells recovered from allogeneic HSCT displayed significantly higher proportions of CD57+ cells compared with healthy controls (HC, median 23% [range 6%-67%]; HSCT 58% [11%-97%]; p= 8.1e−06; Figure 1A-B). Such a difference was detected at early time points after transplantation and further increased at later time points (Figure 1B). After taking into account T cell subsets heterogeneity, we observed higher proportions of CD57+ cells in CD45RA- CCR7+ CD27+ central memory (CM; p= 0.00057), CD45RA- CCR7- CD27+ transitional memory (TM; p=1.1e-05) and CD45RA- CCR7- CD27- effector memory (EM; p=2.6e−06) CD8 T cells from allogeneic HSCT recipients compared with healthy controls. We did not observe any significant differences in CD57 expression in naïve nor in TEMRA CD8 T cells. Phenotypically, CD57+ CD8 T cells from allogeneic HSCT recipients displayed a senescent immunophenotype char