Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation

Abstract

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h + NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

“…The role of NK cells and their alloreactivity in allogeneic hematopoietic SCT (allo-HSCT) is currently controversial for different transplant settings. 1,[9][10][11][12][13][14] Our earlier study confirmed the deleterious role of a killer Ig-like receptor (KIR) ligand mismatch in this haploidentical GIAC protocol. 15,16 A further study also showed that the recovery of NK cells is, and can be used as, an indicator of the clinical outcome after unmanipulated haploidentical transplantation.…”

rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells

“…Variations in NK cell number and phenotype in CB, adult BM and adult PB As previously described, 25 the absolute numbers of NK cells defined as CD3 À //CD16 þ /CD56 þ cells, differ in CB, BM or adult PB cell therapy products. This is mostly the result of a higher number of cells in aphereses than in BM and CB.…”

“…[19][20][21][22][23]25 While results vary between studies, the influence of rhG-CSF has been reported on monocytes, 21 T cells [21][22][23] and NK cells. 20,22,23 There are contradictory reports on changes in the absolute numbers of NK cells and their proportion within total lymphocytes, following rhG-CSF administration.…”

“…In a previous report, 25 we validated a protocol for a detailed phenotypic analysis of donor NK cells, using cryopreserved samples of marrow or blood grafts, and a set of murine monoclonal antibodies directed mostly to NKR. We here present a follow-up of this study, in which we prospectively analysed fresh blood and apheresis samples obtained from normal donors before and after they received rhG-CSF for mobilisation of haematopoietic progenitors.…”

Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes

“…Moreover, the KIR3DL1-specific Z27 mAb 47 also reacts with an activating KIR (likely represented by KIR3DS1). 48 In the latter case, however, the fluorescence intensity is different in NK cells expressing one or another KIR3D receptor. This allows us to distinguish a Z27 dull NK subset (KIR3DS1 ϩ ) from a Z27 bright population (KIR3DL1 ϩ ).…”