In vivo imaging of graft-versus-host-disease in mice

Panoskaltsis‐Mortari, Angela; Price, Alex; Hermanson, John R.; Taras, Elizabeth; Lees, Christopher J.; Serody, Jonathan S.; Blazar, Bruce R.

doi:10.1182/blood-2003-08-2827

Cited by 139 publications

(141 citation statements)

References 23 publications

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“…12 Missing GVHD-inducing capacity of T EM might be explained by limited T-cell expansion in vivo in contrast to naïve T cells, which immediately migrate to secondary lymphoid organs, followed by massive proliferation and subsequent infiltration to GVHD target organs. 6,13 Lack of CCR7 and CD62L expression on CTLs prevents migration to secondary lymphoid organs and further antigenic restimulations, although GVHD induction is only prevented if T-cell entry to all secondary lymphoid organs is impaired. 27 Expression of a 4 b 7 integrins, PSGL-1 and CXCR3 of CTLs, however, might facilitate entry into GVHD target organs but also into inflamed tissues, such as tumors.…”

Section: Discussionmentioning

confidence: 99%

“…5,7,10 After transfer, naïve T cells immediately migrate to secondary lymphoid organs, followed by massive expansion and subsequent infiltration into GVHD target organs. 6,13 Allogeneic priming in the host enables transplanted naïve T cells not only to induce GVHD but also to mediate an efficient anti-tumor response. Despite their lack of GVHDinducing capacity, memory T cells can also eradicate tumor cells, indicating that GVHD induction and tumor elimination are not only dependent on antigen recognition of target cells but might additionally depend on microenvironment, cell numbers and proliferative capacities.…”

Section: Introductionmentioning

confidence: 99%

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In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease

et al. 2011

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Mature donor-derived T cells in allogeneic bone marrow (BM) transplants mediate the graft-versus-tumor (GVT) effect by recognizing alloantigens on leukemic cells. However, alloantigen reactivity towards non-malignant tissues also induces graft-versus-host disease (GVHD). Defining T-cell subpopulations that mediate the GVT effect in the absence of GVHD induction remains a major challenge in allogeneic BM transplantation. In this study, we show that in vitro-generated alloantigen-specific CD8 þ cytotoxic T cells (CTLs) established by weekly stimulation with alloantigen-expressing antigenpresenting cells did not induce GVHD in two major histocompatibility complex-mismatched BM transplantation models, where induction of lethal GVHD is dependent on the presence of either CD4 þ or CD8 þ T cells. Despite their strong alloantigen specificity, transplantation of CTLs did not induce the expression of GVHD-associated cytokines IFN-c and TNF-a or clinical or histological signs of GVHD, and lead to a survival rate of above 90%. However, transplantation of unstimulated CD8 þ T cells, which were not primed by the alloantigen in vitro, induced GVHD in both the transplantation models. Although CTLs were impaired in GVHD induction, they efficiently eradicated Bcr-Abl-transformed B-cell leukemias or mastocytomas. Thus, in vitro-derived CTLs might be useful for optimizing anti-tumor therapy in the absence of GVHD induction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease

et al. 2011

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“…11,12 Defining the specific adhesion molecules involved in this process of lymphocyte trafficking may provide novel opportunities for the monitoring, prophylaxis and treatment of acute GVHD after HCT.…”

Section: Discussionmentioning

confidence: 99%

Expression of α4β7 integrin on memory CD8+ T cells at the presentation of acute intestinal GVHD

McDonough

Chen

et al. 2012

Bone Marrow Transplant

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Acute intestinal GVHD remains a major source of morbidity after allogeneic hematopoietic cell transplantation (HCT). a4b7 integrin is a cell surface molecule that mediates lymphocyte trafficking to intestinal tissue. In this analysis, peripheral blood was collected at the time of presentation of symptoms of acute GVHD and before any treatment. In all, 45 samples were collected and divided into three groups on the basis of subsequent evaluation: intestinal GVHD (n ¼ 15), skin GVHD (n ¼ 20) and no GVHD (n ¼ 10). Two patients developed intestinal GVHD after DLI. The no-GVHD group comprised 10 patients who presented with suspicious symptoms, but evaluation yielded other etiologies. Analysis by flow cytometry showed that intestinal GVHD patients had a significantly higher percentage of a4b7 integrin-expressing memory CD8 þ T cells (median 7.69%; lower and upper quartiles, 1.06% and 11.64%, respectively) compared with patients with skin GVHD (1.26%; 0.57% and 2.49%) and no GVHD (0.96%; 0.44% and 1.85%), P ¼ 0.03. No differences were found in a4b7 expression in any CD4 þ T-cell subsets or naive CD8 þ T cells. This study adds to the evidence that a4b7 integrin is involved in lymphocyte trafficking in acute intestinal GVHD.

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“…37,59 We chose our experimental approach to at least partially recapitulate this initial priming and imprinting phase circumventing the need for trafficking to secondary lymphoid organs. Despite an earlier report that Peyer patches are crucial for the initiation of a graft-versus-host reaction (GVHR), 60 there is evidence that this may not apply to GVHD and that secondary lymphoid organs may compensate for each other.…”

Section: Dendritic Cells Imprint Allogeneic T Cells 2935mentioning

confidence: 99%

Organ-derived dendritic cells have differential effects on alloreactive T cells

Kim¹,

Terwey²,

Zakrzewski³

et al. 2008

Blood

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In vivo imaging of graft-versus-host-disease in mice

Abstract: We have developed a mouse system by which to track the migration and homing of cells in a setting of bone marrow transplantation (BMT)-induced graft-versushost disease (GVHD) after systemic infusion using enhanced green fluorescence protein (

Cited by 139 publications

References 23 publications

In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease

In vitro-established alloantigen-specific CD8+ CTLs mediate graft-versus-tumor activity in the absence of graft-versus-host disease

Expression of α4β7 integrin on memory CD8+ T cells at the presentation of acute intestinal GVHD

Organ-derived dendritic cells have differential effects on alloreactive T cells

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