Alteration in Graft Versus Host Reactivity and in Hematopoietic Stem Cells of Spleen Cell Inocula from Donor Mice Pretreated with Pertussis Antigen

1971 ◽  
Author(s):  
E. A. Eikman ◽  
R. T. Bowser
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Spleen Cell ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Pertussis Antigen

FLT3 ligand promotes engraftment of allogeneic hematopoietic stem cells without significant graft-versus-host disease1

2003 ◽  
pp. 933-940 ◽  
Author(s):  
Murad Y. Yunusov ◽  
George E. Georges ◽  
Rainer Storb ◽  
Peter Moore ◽  
Hans Hagglund ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Flt3 Ligand ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Pure Hematopoietic Stem Cells Reconstitute Immunity in Allogeneic Hosts Superior to Bone Marrow: Immunosuppression by Subclinical Graft-Versus-Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4869-4869
Author(s):  
Gabriel J. Tsao ◽  
Jessica A. Allen ◽  
Kathryn Logronio ◽  
Laura C. Lazzeroni ◽  
Judith A. Shizuru
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cell ◽  
Hematopoietic Stem Cells ◽  
Graft Versus Host Disease ◽  
Immune Reconstitution ◽  
T Cell Depletion ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Allele Specific

Abstract Antigen specific immune responses are known to be impaired following allogeneic hematopoietic cell transplantation (HCT). Some clinical studies suggest that graft T cell depletion for the prevention of graft-versus-host disease (GVHD) leads to poorer immune recovery, while other correlate GVHD with delayed immune reconstitution. Our studies sought to examine the degree to which the co-transplantation of GVHD-inducing mature cells mediated protective immunity post-HCT. We compared the transplant of FACS purified hematopoietic stem cells (HSC: cKit+Thy1.1loSca+Lin-) with bone marrow (BM) between congenic (BA to B6Ly5.2), minor-antigen mismatched (BA to BALB.B), haploidentical (BAxSWR F1 to BALB/cxSWR F1) and MHC-mismatched (BA to BALB/c) donor and host pairs. We show that grafts composed solely of purified HSC give uniformly superior lymphoid reconstitution across all mismatched pairs, both qualitatively and quantitatively. Although absolute blood lymphocytes counts were increased in recipients of BM compared to HSC, lymphoid reconstitution as measured by lymph node size, counts and architecture was significantly improved in the HSC groups regardless of minor or major mismatches between donor and host. Proliferative responses to the allele specific peptides of the antigen hen egg lysozyme were also significantly increased in the HSC as compared BM recipients (p=0.028), with fully MHC mismatched BM recipient cells showing almost no proliferative response. The use of MHC allele specific antigens also revealed that T cell responses post-HCT are dominated by donor-restricted elements. These data suggest that subclinical GVHD mediated by mature cells in the donor BM result in impaired immune reconstitution. While there may be an increase in absolute lymphocyte numbers, this increase does not correlate with an increase in immune cell function. These findings provide important insight into the benefits of purified HSC for preventing post-HCT infectious complication in addition to its known GVHD prophylaxis benefits. Our data highlights the benefit of transplanting a pure HSC population, as the relatively small number of T cells that are found in mouse bone marrow or that remain in the graft after T cell depletion in humans can still result in immune impairment due to subclinical GVHD.

scholarly journals Ex Vivo Gene Therapy: Graft-versus-host Disease (GVHD) in NSG™ (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) Mice Transplanted with CD34+ Human Hematopoietic Stem Cells

2019 ◽  
Vol 47 (5) ◽  
pp. 656-660 ◽  
Author(s):  
Sundeep Chandra ◽  
Patrizia Cristofori ◽  
Carlos Fonck ◽  
Charles A. O’Neill
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Graft Versus Host Disease ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Human Cd34

A therapeutic option for monogenic disorders is gene therapy with ex vivo-transduced autologous hematopoietic stem cells (HSCs). Safety or efficacy studies of ex vivo-modified HSCs are conducted in humanized mouse models after ablation of the murine bone marrow and transfer of human CD34+ HSCs. Engrafted human CD34+ cells migrate to bone marrow and differentiate into various human hematopoietic lineages. A 12-week study was conducted in NSG™ mice to evaluate engraftment, differentiation, and safety of human CD34+ cells that were transduced ( ex vivo) with a proprietary lentiviral vector encoding a human gene (BMRN-1) or a mock (green fluorescent protein) vector. Several mice intravenously injected with naive CD34+ cells or transduced CD34+ cells had variable lymphohistiocytic inflammatory cell infiltrates and microgranulomas in the liver and lungs consistent with graft-versus-host disease (GVHD). Spleen, bone marrow, stomach, reproductive tract, but not the skin had similar inflammatory changes. Ex vivo viral transduction of CD34+ cells did not impact engraftment or predispose to xenogeneic GVHD.

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