Deciphering the biology of KIR2DL3+ T lymphocytes that are associated to relapse in haploidentical HSCT

Abstract

KIR are mainly expressed on NK cells and to a lesser extent on T lymphocytes. Although the KIR NK cell repertoire was well explored in haploidentical Hematopoietic Stem Cell Transplantation (HSCT), KIR T cell compartment remains to be investigated in this context. In this study, the investigation of NK receptors on T lymphocytes during immune reconstitution after T-cell-replete haploidentical HSCT with Post-Transplant Cyclophosphamide (PTCy) has shown a significant increase of KIR2DL2/3+ T cell frequency at day 25. This was especially observed at day 30 in recipients who relapsed. IL-15 but not IL-12 increased in vitro KIR+ T cell expansion suggesting that the raised IL-15 serum concentration observed after PTCy in haploidentical HSCT might increase KIR+ T cell frequency. Moreover, investigations from healthy blood donors showed a higher inhibiting effect of KIR2DL3 on CMV specific T cell response against allogeneic than autologous C1+ target cells. The association of KIR+ T cell subset with relapse may suggest that inhibitory KIR2DL2/3 limit anti-leukemic effect of specific T lymphocytes at this early step of immune reconstitution. Further phenotypic and mechanistic investigations on this cell subset from a broader cohort of HSCT recipients should clarify its potential implication in relapse occurrence. Our results demonstrate that KIR-HLA interactions known to modulate NK cell functions also modulate T cell immune responses in the context of allogeneic HSCT.

Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

“…Evaluation of the composition of post-COVID BAL by scRNAseq revealed that macrophages dominated in all subjects, with smaller T cell, NK T cell, dendritic cell, epithelial and B cell populations also identified (Figure 1b-d and Supplementary Figure 1a-d). Each of the cell types expressed high levels of independently established marker genes (Adams et al, 2020; Cheng et al, 2021; David et al, 2021; Davies et al, 2013; Davis and Wypych, 2021; Gardell and Parker, 2017; Glass et al, 2020; Murray and Wynn, 2011; Tsyklauri et al, 2023; van Aalderen et al, 2021; Villani et al, 2017), validating our annotations (Figure 1d). The notable difference between the two phenotypes was significantly higher abundance of CD4 T cells and CD8 T cells in inflammatory PCLD (Figure 1e).…”

“…Evaluation of the composition of PCLD BAL by scRNAseq revealed that macrophages dominated in all subjects, with smaller T cell, NK T cell, dendritic cell, epithelial and B cell populations also identified (Figure 1C-E and E1A-E). Detected cell types expressed high levels of established marker genes (8)(9)(10)(15)(16)(17)(18)(19)(20)(21)(22), validating our annotation strategy (Figure 1E). The notable difference between the two phenotypes was significantly higher abundance of CD4 T cells and CD8 T cells in inflammatory PCLD (Figure 1F).…”

“…A population with low numbers of genes, which could not be annotated by automatic or manual methods and likely represents empty droplets containing ambient RNA, was removed after clustering. To validate our clustering and annotation strategy, we visualized the expression of canonical or published marker genes for each cell type using a dot plot (Adams et al, 2020; Cheng et al, 2021; David et al, 2021; Davies et al, 2013; Davis and Wypych, 2021; Gardell and Parker, 2017; Glass et al, 2020; Murray and Wynn, 2011; Tsyklauri et al, 2023; van Aalderen et al, 2021; Villani et al, 2017).…”

Killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands in a Brazilian population

“…Correlations related to the treatment of patients with HCV and also to the overall survival of bone marrow transplant patients have already been described with KIR 2DL2/3 binding with HLA group C1. 57 , 58 …”

“…Correlations related to the treatment of patients with HCV and also to the overall survival of bone marrow transplant patients have already been described with KIR 2DL2/3 binding with HLA group C1. 57,58 One to four inhibitory KIR/HLA pairs were determined (Table 3). The presence of two pairs was more frequent (42.7%), followed by three pairs (32.6%), one pair (16.5%), and four pairs (7.9%).…”