scholarly journals MyD88 Signaling in CD4 T Cells Promotes IFN-γ Production and Hematopoietic Progenitor Cell Expansion in Response to Intracellular Bacterial Infection

2013 ◽  
Vol 190 (9) ◽  
pp. 4725-4735 ◽  
Author(s):  
Yubin Zhang ◽  
Maura Jones ◽  
Amanda McCabe ◽  
Gary M. Winslow ◽  
Dorina Avram ◽  
...  
Keyword(s):  
T Cells ◽  
Bacterial Infection ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Ifn Γ ◽  
Myd88 Signaling

scholarly journals The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation

Blood ◽  
2013 ◽  
Vol 122 (3) ◽  
pp. 376-385 ◽  
Author(s):  
Brenden W. Smith ◽  
Sarah S. Rozelle ◽  
Amy Leung ◽  
Jessalyn Ubellacker ◽  
Ashley Parks ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Blood Products ◽  
Hematopoietic Progenitor ◽  
Aryl Hydrocarbon ◽  
Key Points

Key Points This breakthrough involves the role of the aryl hydrocarbon receptor in the expansion and specification of hematopoietic progenitor cells. This work sets a precedent for the use of an in vitro platform for the clinically relevant production of blood products.

Ex Vivo Hematopoietic Progenitor Cell Expansion

ImmunoMethods ◽  
1994 ◽  
Vol 5 (3) ◽  
pp. 217-225 ◽  
Author(s):  
D.N. Haylock ◽  
S. Makino ◽  
T.L. Dowse ◽  
S. Trimboli ◽  
S. Niutta ◽  
...  
Keyword(s):  
Cell Expansion ◽  
Progenitor Cell ◽  
Ex Vivo ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor

Prognostic Analysis of Pre-Transplant CD26-Positive Lymphocytes and CD26bright/CD45RO-Positive Memory T-Cell Levels in Patients Receiving an Autologous Hematopoietic Progenitor-Cell Transplant.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1653-1653
Author(s):  
Martin Hildebrandt ◽  
Hella Gollasch ◽  
Kirstin Rautenberg ◽  
Bernd Doerken ◽  
Wolf-Dieter Ludwig
Keyword(s):  
T Cells ◽  
T Cell ◽  
Progenitor Cell ◽  
Memory T Cells ◽  
Cell Subset ◽  
Hematopoietic Progenitor Cell ◽  
Cell Transplant ◽  
Hematopoietic Progenitor ◽  
Memory T Cell ◽  
Kinetics Of

Abstract The lymphocyte surface glycoprotein CD26 is involved in an array of diverse signalling pathways and costimulatory events. CD26positive cells possess dipeptidylpeptidase IV (DPP IV) activity, a serine protease known to inactivate SDF-1/CXCL12, a key mediator of stem cell homing and engraftment. Furthermore, CD26 modulates surface expression of CTLA-4 and contributes to T-cell migration through endothelial layers. CD26 has been attributed with a central role in alloantigen-mediated immune pathways and memory T-cell responses. The purpose of this study was to evaluate the levels of a distinct memory T-cell subset, CD26bright/CD45RO-positive, in autologous hematopoietic progenitor-cell transplant (HPCT) recipients. Between 2003 and 2006 we enrolled 42 patients scheduled to undergo high-dose chemotherapy and autologous HPCT (multiple myeloma, n=31; Hodgkin’s Disease, n=3; NHL, n=6; PNET, n=1; AML, n=1). Levels of memory and naïve CD26, CD34, CD4, CD8, as well as co-expression of CD4 or CD8 among CD26bright/CD45RO-positive cells were analyzed before autologous HPCT. In addition, the number of memory and naïve CD26-positive T cells transfused per kg body weight in the progenitor cell harvest were determined. The subsets of CD26-positive cells were correlated with kinetics of engraftment and with the occurrence of disease progression or relapse after autologous transplantation. With regard to kinetics of engraftment, only the number of CD34-positive cells transfused was associated with rapid engraftment (P=0.001). However, CD26-positive cells were of predicitve value for the occurrence of disease progression or relapse. Pre-transplant CD26-positive T-cell levels correlated with progression-free survival (PFS) (P=0.022). Specifically, the number of CD26bright/CD45RO-positive memory T-cells in the autograft correlated with PFS and, in regression analyses, emerged as the only variable predictive for the occurrence of diease progression or relapse (P=0.006). The prognostic effects of pre-transplant CD26bright/CD45RO-positive memory T-cells were independent of the type of disease and of the conditioning regimen applied. The analysis of antigens CD4 and CD8, respecively, on CD26bright/CD45RO-positive T-cells yielded no additional information. Our results suggest that pre-transplant levels of CD26-positive T cells, specifically a memory cell subset of CD26bright cells coexpressing CD45RO, may yield information with regard to outcome in autologous HPCT recipients. These observations may contribute to a prospective identification of those patients at higher risk of relapse, based on their immune status.

scholarly journals Wnt4 Enhances Murine Hematopoietic Progenitor Cell Expansion Through a Planar Cell Polarity-Like Pathway

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e19279 ◽  
Author(s):  
Krista M. Heinonen ◽  
Juan Ruiz Vanegas ◽  
Deborah Lew ◽  
Jana Krosl ◽  
Claude Perreault
Keyword(s):  
Cell Polarity ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Planar Cell Polarity ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor

Predictors of More Rapid Lymphoid Reconstitution after Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3159-3159
Author(s):  
Martha L. Arellano ◽  
Susan G. Moore ◽  
Ragini Kudchadkar ◽  
Christopher R. Flowers ◽  
Amelia A. Langston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Progenitor Cell ◽  
T Cell Subsets ◽  
Hematopoietic Progenitor Cell ◽  
Gamma Delta ◽  
Median Dose ◽  
Hematopoietic Progenitor ◽  
Post Transplant ◽  
Cd34 Cells

Abstract Introduction: Aberrant post-transplant immune reconstitution contributes to the major risks of graft versus host disease (GVHD), infection, and relapse following allogeneic hematopoietic progenitor cell transplantation. Faster lymphocyte engraftment has been found to predict better clinical outcomes in patients after autologous and allogeneic bone marrow transplantation. The purpose of our study was to investigate factors that may contribute to more rapid lymphocyte engraftment in patients who underwent transplantation using grafts procured from HLA-matched volunteer unrelated donors. Methods:We analyzed 47 recipients of BM (n=13) and G-CSF mobilized blood hematopoietic progenitor cell grafts (n=34) for post-transplant lymphoid reconstitution, and constituents of the graft that predicted early lymphoid recovery. Diagnoses included 28 patients with AML/MDS/MPD, 6 with lymphoma/CLL, 6 with ALL, 3 with CML, 2 with MM and 2 with AA, with a median age of 43 years (range 17–68). 34 patients received TBI or busulfan-based myeloablative regimens; 13 patients received fludarabine and low-dose TBI. Numbers of T-cell, NK, B-cell, and dendritic cell subsets in the grafts were enumerated by flow cytometry. Our primary end point was lymphocyte engraftment at day+30 (ALC > 500 x 2 days). Secondary analyses included: univariate and multivariate models exploring the relationship between graft constituents and early lymphoid recovery. Results: With a median follow-up of 1 year (range 1–32 months), 11 (23%) patients died prior to lymphocyte engraftment; 2 patients failed to achieve ALC > 500; and 20 (43%) patients were alive with stable lymphocyte engraftment. The median dose of CD34+ cells administered was 5.35 x 10E6 cells/kg; and the median dose of CD3+ cells was 211 x 10E6 cells/kg.The mean absolute lymphocyte count (ALC) on day +30 for the entire group was 714 ± 125 cells per mcL, with a median time to achieve an ALC > 500/mcL for 2 consecutive days of 23 days (range 0–111 days). In univariate analyses, higher doses of the following T-cell subsets in the graft were predictive of faster lymphocyte engraftment (all x 10E6 cells/kg): CD3+ > 296 (p=0.01), CD4+ > 172 (p=0.04), CD123+11c- (DC2) > 3.38 (p=0.03), and gamma-delta T- cells > 5.50 (p=0.01). The graft content of CD34+ cells and other graft constituents were not significantly associated with faster lymphoid engraftment. Stepwise multivariate Cox regression models including all graft constituents, conditioning regimen and patient characteristics determined that gamma-delta T-cell dose in the graft was the only factor associated with faster lymphocyte engraftment (p < 0.01). Faster lymphocyte engraftment was not significantly associated with CMV reactivation, or the incidence of either acute or chronic GVHD. Conclusions: The kinetics of lymhoid reconstitution following allogeneic volunteer unrelated donor transplantation are associated with the content of donor T-cells and DC2 in the graft. Faster lymphoid reconstitution was not associated with less CMV infection nor improved survival in this relatively small population. Ongoing studies are examining the role of lymphoid reconstitution in post-transplant outcomes in a larger data base of allogeneic transplant recipients.

CD4+ Perforin+ T Cells in B-CLL: MHC Class II Restriction and Anti-Cytomegalovirus Reactivity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4979-4979
Author(s):  
James Walton ◽  
Keirissa Lawson ◽  
Maria S. Manoussaka ◽  
Amit Nathwani ◽  
Vincent Emory ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Class Ii ◽  
Cd4 Cells ◽  
Hla Dr ◽  
Ifn Γ ◽  
T Cell Expansion

Abstract Introduction: An expansion of CD4+ T cells expressing perforin (PF) has recently been described in B-CLL and we have previously demonstrated anti-cytomegalovirus (CMV) reactivity within this population (Walton et al; 2004; Blood [ASH annual meeting abstracts] 104:4787). Here we further characterise the anti-CMV response of CD4+PF+ T cells in B-CLL and investigate the role of CMV in CD4+PF+ T cell expansion. Methods: Peripheral blood mononuclear cells (PBMC’s) from 24 untreated B-CLL patients (17 CMV seropositive [SP], 7 CMV seronegative [SN]), 2 SP treated (Campath) patients and 12 healthy age-matched control individuals (8 SP, 4 SN) were fixed, permeabilised and stained with anti-CD4PerCP, anti-IFN-γ-APC and anti-PF-FITC monoclonal antibodies (mABs) (BD). PBMC were cultured for 18 hrs with DOWNE cell lysate (Dade Behring) containing CMV-antigen or lysate alone and with anti-CD28 and anti-CD49d mAbs (BD), in the presence of Brefeldin A (eBiosciences). In blocking experiments PBMC were pre-incubated with anti-HLA DR,DP,DQ mAb (BD) for 1 hour. The CMV specific response was assessed by flow cytometry (Dako Cyan, Summit software) as the percentage of IFN-γ+ cells in PF+ and PF− CD4+ T cell populations. Statistical analysis was performed using the Mann-Whitney U test and Spearman rank correlation. Results: The proportion of CD4+ T cells expressing PF directly ex vivo was significantly higher in SP B-CLL patients (17.5±18.6%) compared to SN patients (2.0±2.3%, p=0.019). In seropositive aged matched controls the percentage of CD4+ cells expressing perforin was positively correlated with the percentage of CMV-reactive CD4+ cells (r=0.976, p&lt;0.01). In contrast, there was no significant correlation in the patient group. However, two patients with relatively large expansions of CD4+PF+ cells (37.7±3.39%) post-Campath treatment had high percentages of CMV-reactive CD4+ cells (10.93±0.62%) compared to SP B-CLL patients (1.34±1.19%) and SP controls (1.31±1.14%), implying Campath related CMV reactivation. The addition of anti-HLA-DR,DP,DQ mAb to patients’ PBMCs, prior to CMV stimulation, led to an 80% (from 3.26% to 0.79%) and 90% (from 3.9% to 0.45%) reduction in the proportion of antigen reactive CD4+ and CD4+PF+ cells respectively. Conclusions: A population of major histocompatibility complex (MHC) class II restricted, CMV reactive, CD4+PF+ T cells exists peripherally, in a large group of CMV SP B-CLL patients. Furthermore, CMV is associated with CD4+PF+ T cell expansion in patients and controls. Our data implies that high numbers of B-CLL cells inhibit anti-viral effector function, leading to increased viral activity and chronic antigenic exposure, potentially driving CD4+PF+ T cell expansion.

scholarly journals Hematopoietic progenitor cell regulation by CD4+CD25+ T cells

Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4934-4943 ◽  
Author(s):  
Maite Urbieta ◽  
Isabel Barao ◽  
Monica Jones ◽  
Roland Jurecic ◽  
Angela Panoskaltsis-Mortari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Activity ◽  
Innate Immune ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem

Abstract CD4+CD25+FoxP3+ regulatory T cells (Tregs) possess the capacity to modulate both adaptive and innate immune responses. We hypothesized that Tregs could regulate hematopoiesis based on cytokine effector molecules they can produce. The studies here demonstrate that Tregs can affect the differentiation of myeloid progenitor cells. In vitro findings demonstrated the ability of Tregs to inhibit the differentiation of interleukin-3 (IL-3)/stem cell factor (colony-forming unit [CFU]-IL3)–driven progenitor cells. Inhibitory effects were mediated by a pathway requiring cell-cell contact, major histocompatibility complex class II expression on marrow cells, and transforming growth factor-β. Importantly, depletion of Tregs in situ resulted in enhanced CFU-IL3 levels after bone marrow transplantation. Cotransplantation of CD4+FoxP3+gfp Tregs together with bone marrow was found to diminish CFU-IL3 responses after transplantation. To address the consequence of transplanted Tregs on differentiated progeny from these CFU 2 weeks after hematopoietic stem cell transplantation, peripheral blood complete blood counts were performed and examined for polymorphonuclear leukocyte content. Recipients of cotransplanted Tregs exhibited diminished neutrophil counts. Together, these findings illustrate that both recipient and donor Tregs can influence hematopoietic progenitor cell activity after transplantation and that these cells can alter responses outside the adaptive and innate immune systems.

Sign in / Sign up

Export Citation Format

Share Document