Graft-versus-Host-Reactions: A Review

Sc, Grebe; Jw, Streilein

doi:10.1016/s0065-2776(08)60549-0

Cited by 189 publications

(49 citation statements)

References 489 publications

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“…These results are consistent with prior studies conducted many years ago in nonirradiated parent3F1 (first filial generation) models of GVHD in which serial transfer of GVHD occurred only when massive numbers of cells were administered to secondary recipients. 18 Since tissue damage is a progressive and ongoing event in GVHD, this suggests that propagation of GVHD must be dependent upon an alternative pathway of allorecognition. Our data demonstrating that equivalent For personal use only.…”

Section: Discussionmentioning

confidence: 99%

Emergent autoimmunity in graft-versus-host disease

Tivol

Komorowski

Drobyski

2005

Blood

112

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Donor T-cell recognition of host alloantigens presented by host antigen-presenting cells (APCs) is necessary for the induction of graft-versus-host disease (GVHD), but whether direct alloreactivity is sufficient for the propagation of GVHD is unknown. In this study, we demonstrate that GVHD cannot be effectively propagated through the direct pathway of allorecognition. Rather, donor T-cell recognition of antigens through the indirect pathway is necessary for the perpetuation of GVHD. Furthermore, GVHD results in the breaking of self tolerance, resulting in the emergence of donor T cells that can cause autoimmune disease in syngeneic recipients. Notably, GVHD-induced autoreactivity is donor APC dependent, transferable into secondary hosts, and involves cells of the innate immune system.

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Section: Discussionmentioning

confidence: 99%

Emergent autoimmunity in graft-versus-host disease

Tivol

Komorowski

Drobyski

2005

Blood

112

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“…The studies reported here were performed with the aim of identifying in which brain areas c-Fos IR is detected during the course of a GvHR, a model of an specific immune response to host antigens [21][22][23]. Using this approach, neurons from several brain areas, particularly from the cerebral cortex, were shown to express c-Fos IR during the induction phase of GvHR.…”

Section: Introductionmentioning

confidence: 99%

c-Fos Expression in the Rat Cerebral Cortex during Systemic GvH Reaction

Furukawa

Yamashita

Rey

et al. 2004

Neuroimmunomodulation

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Objective: It is becoming clear that the CNS receives signals from the peripheral immune system. In order to identify the areas of the brain that receive information about a specific immune response to allogeneic antigens, we studied the expression of c-Fos, a neural activation marker, in the cerebral cortex following the induction of a graft-vs.-host reaction (GvHR) in rats. Methods: C-Fos expression in the brain was studied by immunohistochemistry. GvHR was induced in (WKY × PVG)F₁ rats by injecting 5 × 10⁸ spleen cells from PVG rats. Control rats received syngeneic cells. Results: No c-Fos immunoreactivity (IR) was observed in animals undergoing GvHR in the nucleus tractus solitarii (NTS), the locus coeruleus (LC), the organum vasculosum of lamina terminalis (OVLT), the paraventricular nucleus (PVN) or the central amygdaloid nucleus (Ce). In contrast, 3 days after GvH induction c-Fos IR was observed in the piriform cortex and several other olfactory-related regions indicating the stimulation of the olfactory pathway during GvHR. Strong c-Fos IR was also observed in the occipital visual cortex of animals undergoing a GvHR, suggesting that GvHR can affect visual functions. In addition, GvHR induced c-Fos IR in the prefrontal cortex (Cg3, orbital cortex), a region that has interconnections with most sensory modalities. Double-staining studies indicate that the cells that express the c-Fos signal are neurons. Conclusion: We have defined the distribution of brain neurons that are affected during the induction phase of GvHR. Our results also indicate that the integration and processing of information from the immune system at CNS levels involve different areas during different types of immune responses.

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“…[5][6][7][8][9] It is assumed that both graft-versus-host disease (GVHD) and GVL, being observed together and considered to be inseparable at this point, are mediated by specific or nonspecific allocellular immunity. [10][11][12] Thus, the grade of GVHD may be considered as a surrogate marker for the GVL effect, and an appropriate level of GVL (or GVHD) should be sought according to the condition of the underlying disease. It is a general understanding that grade I acute GVHD may be associated with an improved post-transplant outcome.…”

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confidence: 99%

Clinical impact of graft-versus-host disease against leukemias not in remission at the time of allogeneic hematopoietic stem cell transplantation from related donors. The Japan Society for Hematopoietic Cell Transplantation Working Party

Kataoka¹,

Kami²,

Takahashi

et al. 2004

Bone Marrow Transplant

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Summary:Acute graft-versus-host disease (GVHD) increases posttransplant mortality and morbidity, but exerts a potent graft-versus-leukemia (GVL) effect. To clarify the impact of GVHD on outcome after transplant in aggressive diseases, patients with acute myeloid or lymphoblastic leukemia (AML, n ¼ 366 or ALL, n ¼ 255) in nonremission states, or chronic myelogenous leukemia (CML, n ¼ 180) in accelerated phase (AP) or blastic crisis (BC), who received allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor between 1991 and 2000, were analyzed. Significant improvement in overall and disease-free survival (DFS) was detected with grade I acute GVHD in AML (P ¼ 0.0002 for overall survival and 0.0009 for DFS, respectively) and in CML (P ¼ 0.0256 and 0.0366, respectively), while the trend towards improved survival was observed in ALL. Relapse rate was lower in grade I acute GVHD than in grade II in all three diseases, suggesting that treatment for grade II GVHD may compromise the GVL effect associated with GVHD. Chronic GVHD was found to suppress relapse in CML and ALL, but not in AML, although no improvement in survival was observed in any disease category. Our results suggest that treatment for grade II acute GVHD may need to be attenuated in transplant for refractory leukemias. Refractory or relapsed acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML) in accelerated phase (AP) or blastic crisis (BC) have poor prognosis, and conventional salvage chemotherapy does not yield satisfactory survival benefit for patients with these refractory and/or advanced leukemias. If a suitable donor for allogeneic hematopoietic stem cell transplantation (HSCT) is available and the patient's general condition permits, high-dose chemoradiotherapy followed by allogeneic HSCT is indicated for the advanced stage of these diseases. In spite of high incidence of transplant-related mortality (TRM) and morbidity, including regimen-related toxicity (RRT), infection, and other complications, 1,2 allogeneic HSCT during the nonremission state seems to contribute toward prolonged disease-free survival (DFS). Indeed, clinical

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Graft-versus-Host-Reactions: A Review

Cited by 189 publications

References 489 publications

Emergent autoimmunity in graft-versus-host disease

Emergent autoimmunity in graft-versus-host disease

c-Fos Expression in the Rat Cerebral Cortex during Systemic GvH Reaction

Clinical impact of graft-versus-host disease against leukemias not in remission at the time of allogeneic hematopoietic stem cell transplantation from related donors. The Japan Society for Hematopoietic Cell Transplantation Working Party

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