The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Ho, Vincent T.; Soiffer, Robert J.

doi:10.1182/blood.v98.12.3192

Cited by 388 publications

(306 citation statements)

References 186 publications

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“…The graft failure observed in T-cell-depleted BMT patients is believed to be a consequence of grafted cells' rejection by the host immune system. 20,56 Experimental models using mixed radiation chimeras showed that bone marrow engraftment is dependent on the presence of T cells syngeneic to the graft. 57 Similar results were found in human studies with patients under nonmyeloablative regimen, that is, T-cell donor chimerism higher than 90% is required for donor cell engraftment to occur.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, BM engraftment after bone marrow transplantation (BMT) has been shown to depend on T cells, since T-cell-depleted allogeneic BMT (for graft versus host disease [GVHD] prophylaxis) increases the risk of graft failure in about 70% in clinical and experimental approaches. 19,20 Complete posttransplantation recovery and HSC maintenance in different animal models suggest a major histocompatibility complex (MHC) class II dependency 21,22 and imply a role for CD4 ϩ T cells in hematopoietic recovery.…”

Section: Introductionmentioning

confidence: 99%

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Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Monteiro

Benjamin

Costa

et al. 2005

Blood

105

104

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Monteiro

Benjamin

Costa

et al. 2005

Blood

105

104

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“…Although the reason for this is unknown, it may be due to the transfer of a significantly larger dose of mature, immunocompetent T cells. Until now, two mechanisms have been suggested for the pathogenesis of chronic GVHD (1,2). One is alloreactivity to minor histocompatibility Ags, and the other is a role of postthymic CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

“…G raft-vs-host disease (GVHD) 3 is a well-recognized complication of allogeneic bone marrow transplantation and is a major impediment to its overall therapeutic success (1,2). In recent years, peripheral blood stem cells have largely replaced bone marrow as a peripheral source of allogeneic stem cells because of their relative ease of collection, quicker engraftment kinetics, and economic advantages.…”

Section: Antagonist Of Secondary Lymphoid-tissue Chemokine (Ccr Liganmentioning

confidence: 99%

Antagonist of Secondary Lymphoid-Tissue Chemokine (CCR Ligand 21) Prevents the Development of Chronic Graft-Versus-Host Disease in Mice

Sasaki

Hasegawa

Kohno

et al. 2003

The Journal of Immunology

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The use of receptor antagonists for chemokines is an alternative approach to blocking chemokine actions and has the potential to provide novel therapeutics. We determined the receptor antagonist properties of murine N-terminally truncated secondary lymphoid tissue chemokine (SLC)/6Ckine/CCR ligand 21 analogs and evaluated the preventive effects of SLC antagonists on chronic graft-vs-host disease (GVHD) in a murine model by blocking the homing of donor CCR7-expressing T cells into the recipient’s lymphoid organs. SLC analogs truncated >4 aa residues from the N terminus showed a loss of chemotaxis and Ca2+ influx of CCR7-expressing cells and also inhibited SLC-stimulated chemotaxis and SLC-induced Ca2+ influx completely. To determine whether SLC antagonist inhibits the development of chronic GVHD, chronic GVHD was induced by injecting DBA/2 spleen cells into (C57BL/6 × DBA/2) F1 mice. Total numbers of spleen cells and host B cells, serum levels of IgE, and of total IgG and IgG1 of anti-DNA Abs in SLC antagonist-treated GVHD mice were significantly lower than those in control PBS-treated GVHD mice. This was due to a reduction in the levels of activated donor CD4+ T cells and a decrease in IL-4 production, resulting in a reduction in the numbers of activated host B cells. Therefore, our results suggest that SLC antagonist has beneficial effects for the prevention of chronic GVHD.

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“…Immunosuppressive drugs that impair T cell function or T cell depletion of the graft can decrease the incidence of GvHD [5]. However, this GvHD prophylaxis has several adverse effects, especially in adults with diminished thymic function.…”

Section: Introductionmentioning

confidence: 99%

Alloreactive CD4 T lymphocytes responsible for acute and chronic graft‐versus‐host disease are contained within the CD45RC^high but not the CD45RC^low subset

et al. 2004

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Graft-versus-host disease (GvHD) is a major complication of allogeneic bone marrow transplantation and occurs when donor T cells react with histo-incompatible recipient's antigens. In the present study, we analyzed the contribution of CD4 T cell subsets, defined according to their CD45RC expression level, in the development of acute and chronic GvHD. For this purpose, we used the model of GvHD induced in rats when parental lymphocytes are transferred to irradiated (LEW×BN) F1 hybrid recipients. We showed that parental CD45RC high (naive cells) CD4 T cells induced both acute and chronic GvHD while CD45RC low (memory cells) subset did not. In vitro, only CD45RC high CD4 T cells proliferated and produced cytokines in response to alloantigen stimulation. LEW and BN CD45RC high CD4 T cells produced different cytokine profiles in response to in vitro allostimulation, which could explain their ability to induce different forms of GvHD. Finally, we showed that memory CD45RC low CD4 T cells, known to contain regulatory T cells, were unable to prevent GvHD induction. Together these data show that memory CD45RC low CD4 T cells do not contain functional alloreactive T cells and suggest that selective transfusion of donor memory cells could greatly improve post-transplant immune reconstitution without risk of GvHD induction.

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The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Cited by 388 publications

References 186 publications

Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Antagonist of Secondary Lymphoid-Tissue Chemokine (CCR Ligand 21) Prevents the Development of Chronic Graft-Versus-Host Disease in Mice

Alloreactive CD4 T lymphocytes responsible for acute and chronic graft‐versus‐host disease are contained within the CD45RC^high but not the CD45RC^low subset

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The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Cited by 388 publications

References 186 publications

Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells

Antagonist of Secondary Lymphoid-Tissue Chemokine (CCR Ligand 21) Prevents the Development of Chronic Graft-Versus-Host Disease in Mice

Alloreactive CD4 T lymphocytes responsible for acute and chronic graft‐versus‐host disease are contained within the CD45RChigh but not the CD45RClow subset

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Alloreactive CD4 T lymphocytes responsible for acute and chronic graft‐versus‐host disease are contained within the CD45RC^high but not the CD45RC^low subset