Recovery of Vα24+ NKT cells after hematopoietic stem cell transplantation

Abstract

Summary:Human Va24 þ natural killer T (NKT) cells have an invariant T-cell receptor-a chain and are activated in a CD1d-restricted manner. Va24 þ NKT cells are thought to regulate immune responses and to play important roles in the induction of allograft tolerance. In this report, we analyzed the recovery of Va24 þ NKT cells after hematopoietic stem cell transplantation and its correlation with graft-versus-host disease (GVHD). Patients who received a dose-reduced conditioning regimen, antithymocyte globulin-or CAMPATH-1H-containing conditioning regimen were excluded. NKT cells were reconstituted within 1 month after transplantation in peripheral blood stem cell transplantation recipients, while their numbers remained low for more than 1 year in bone marrow transplantation (BMT) recipients. The number of Va24 þ NKT cells in BMT recipients with acute GVHD was lower than that in patients without acute GVHD, and both the CD4 þ and CD4 À Va24 þ NKT subsets were significantly reduced. With regard to chronic GVHD, BMT recipients with extensive GVHD had significantly fewer Va24 þ NKT cells than other patients. Furthermore, the number of CD4 þ Va24 þ NKT cells was also significantly reduced in patients with chronic extensive GVHD. Our results raise the possibility that the number of Va24 þ NKT cells could be related to the development of GVHD.

Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4− Subset Dynamics and Correlates with Remission State

“…Only two studies so far have addressed iNKT cell reconstitution after allogeneic HSCT and demonstrated that iNKT cells emerged and reconstituted to normal values before T cells. The possible correlation between iNKT cell reconstitution and remission was not addressed, although one study suggested that a low number of iNKT cells could be related to the development of GVHD (36). Both studies were performed in adult patients receiving either T cell-replete HLA-matched allogeneic HSC or umbilical cord blood (36,37), and thus required posttransplantation treatment with immune-suppressive drugs to prevent GVHD.…”

“…The possible correlation between iNKT cell reconstitution and remission was not addressed, although one study suggested that a low number of iNKT cells could be related to the development of GVHD (36). Both studies were performed in adult patients receiving either T cell-replete HLA-matched allogeneic HSC or umbilical cord blood (36,37), and thus required posttransplantation treatment with immune-suppressive drugs to prevent GVHD. This faster iNKT cell reconstitution dynamics could depend, at least in patients given HLA-matched HSC, on the adoptive transfer of donor-derived mature lymphocytes present in the graft and/or the different transplantation protocols used in these studies, as compared with our approach of T cell depletion of the graft.…”

Human invariant Vα24+ natural killer T cells acquire regulatory functions by interacting with IL-10–treated dendritic cells

“…3 Human iNKT cells have been implicated in the regulation of autoimmune responses in various diseases [4][5][6] (ie, type 1 diabetes, 7-9 multiple sclerosis, 10,11 and others 12,13 ) and graft-versus-host disease (GVHD). 14 Patients with autoimmune diseases or GVHD typically have reduced frequency of iNKT cells [7][8][9][10][11][12][13][14] with reduced capacity to produce Th2 cytokines, including IL-4 and IL-10. [7][8][9][10][11] The secretion of Th2 cytokines polarizes naive T cells toward a Th2 response and is thought to shift the balance from a pathogenic Th1 toward a protective Th2 response in Th1-dominant autoimmunity.…”

Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression

“…There is only one study 82 that has examined the frequencies of total as well as CD4 + and CD4 − iNKTs in donor PBSC grafts. In a previous study, 80 there was a significant difference in the number of reconstituted iNKTs in patients who received BMT and PBSC. The only variable associated with the number of iNKTs was the stem cell source (peripheral blood or BM).…”

“…79 Second, both CD4 + and CD4 − subsets of iNKTs (Table 1) are reduced in patients with acute GvHD. 80 Third, enhanced iNKT reconstitution post transplantation has been shown to be a predictive factor for an improved overall survival associated with reduction in GvHD without abrogation of the GvL effect. 81 Fourth, lower numbers of CD4 − iNKTs in the donor graft is associated with clinically significant GvHD in patients undergoing HLA-identical allogeneic HSCT.…”