CYTOTOXICITY IN GRAFT-<i>VERSUS</i>-HOST REACTION

Singh, Jagat N.; Sabbadini, E; Sehon, A.H.

doi:10.1084/jem.136.1.39

Cited by 30 publications

(4 citation statements)

References 12 publications

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“…It has been shown that during a GVHR the host cells are activated and capable of lysing parental cells nonspecifically and that parental tumor cells exposed in vitro to spleen cells from F, hybrid mice undergoing a GVHR had a markedly decreased ability to grow in syngeneic recipients (9). Our findings would indicate that similar reactivity against parental cells can be demonstrated in the serum of animals recovering from GVH disease.…”

Section: Discussionsupporting

confidence: 67%

Serum-mediated inhibition of graft-vs.-host reaction.

Cauchi¹,

Dawson²

1975

The Journal of Experimental Medicine

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Rats recovering from a systemic graft-vs.-host reaction (GVHR) possess factors in the serum which can inhibit the production of a local GVHR. After incubation in vitro for 1 h at 37 degrees C these factors reduce the GVH-producing potential of parental spleen or lymph node cells to 24% of control cells treated with normal serum. These factors appear within 1 wk after initiation of a systemic GVHR and some residual activity persists for up to 8 mo. The serum activity was present in the globulin fraction and was completely removed by absorption with spleen, lymph node, or kidney homogenates from either parental strain rats. These studies indicate that during the course of a systemic GVHR, serum factors directed against the host appear in the circulation and tend to inhibit the production of further GVHR by a second challenge of either parental strain cells.

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Section: Discussionsupporting

confidence: 67%

Serum-mediated inhibition of graft-vs.-host reaction.

Cauchi¹,

Dawson²

1975

The Journal of Experimental Medicine

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“…Prominent among the latter phenomena is the socalled "cytokine storm" that results from immune activation, following not only the allogeneic interactions between host and donor cells but also the tissue injury secondary to concurrent infections or preparative regimens [26][27][28]. The nonspecific cytotoxicity in GVHD was found to be related mainly to host rather than donor cells, most prominently macrophages [25,29]. Consequently, the complexity of the immunologic processes that then lead to the "typical" histologic features of GVHD can help explain why GVHD-like changes can be observed in an increasing number of processes that have immunologic dysregulation as a common denominator.…”

Section: Discussionmentioning

confidence: 99%

Histologic Features of Mycophenolate Mofetil-Related Colitis: A Graft-Versus-Host Disease-Like Pattern

Cangro²,

et al. 2003

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Mycophenolate mofetil (MMF) is widely used for maintenance immunosuppression in solid organ transplantation. Gastrointestinal toxicity, usually manifested as diarrhea, is the most common side effect of MMF. We evaluated colonic biopsies from 20 renal transplant patients with MMF-related diarrhea. The latter was defined by the absence of any other demonstrable etiology and improvement or resolution of symptoms by the discontinuation or reduction of the dose of MMF alone. These biopsies were compared with colon biopsies from patients with the following: acute graft-versus-host disease (GVHD, n=10), inflammatory bowel disease (IBD) or infectious colitis (n=10), and colon biopsies from renal transplant patients not receiving MMF (n=8). Normal colonic segments from surgical specimens served as normal controls (n=5). Colonic biopsies from patients with MMF-related diarrhea showed prominent crypt cell apoptosis and reactive/reparative changes including enterocyte cytologic atypia, increased neuroendocrine cells, and glandular architectural distortion. The changes were similar, although of milder degree to the ones seen in patients with acute intestinal GVHD. This pattern of injury was not seen in controls or in biopsies from transplant patients not receiving MMF, and it was markedly different from the one seen in idiopathic inflammatory or infectious colitis. The severity of histologic changes correlated significantly with the endoscopic degree of "colitis." There was no statistically significant correlation between histologic damage and the dose of MMF (corrected for body weight and renal function). MMF-related colitis is a distinct entity that displays histologic features remarkably similar to the ones associated with intestinal GVHD. This form of injury could be related to either direct toxicity or an "innocent by-stander" phenomenon secondary to the alteration of the immunologic microenvironment of the colon caused by the MMF.

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“…It has been previously shown that elimination of host B cells in this model of acute GVHD is mediated by donor anti-host CD8 + CTLs (14,18). Defective elimination of host B cells in pfp→F1 mice cannot be explained by reduced numbers of CD8 + T cells in the B6pfp donor inoculum as the percentage of CD8 + T cells in the donor inocula from five independent experiments did not differ significantly between B6wt and B6pfp mice (wt =7.1 ± 0.4% vs. pfp = 5.7% ± 0.8; n = 5, P = not significant [NS]).…”

Section: Defective Elimination Of Host B Cells In Pfp→f1 Mice Is Not mentioning

confidence: 99%

Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity

Shustov¹,

Luzina²,

Nguyen³

et al. 2000

J. Clin. Invest.

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To determine the role of perforin-mediated cytotoxic T lymphocyte (CTL) effector function in immune regulation, we studied a well-characterized mouse model of graft-versus-host disease (GVHD). Induction of acute GVHD using perforin-deficient donor T cells (pfp→F1) initially resulted in features of acute GVHD, e.g., engraftment of both donor CD4 + and CD8 + T cells, upregulation of Fas and FasL, production of antihost CTL, and secretion of both Th1 and Th2 cytokines. Despite fully functional FasL activity, pfp donor cells failed to totally eliminate host B cells, and, by 4 weeks of disease, cytokine production in pfp→F1 mice had polarized to a Th2 response. Pfp→F1 mice eventually developed features of chronic GVHD, such as increased numbers of B cells, persistence of donor CD4 T cells, autoantibody production, and lupuslike renal disease. We conclude that in the setting of B-and T-cell activation, perforin plays an important immunoregulatory role in the prevention of humoral autoimmunity through the elimination of both autoreactive B cells and ag-specific T cells. Moreover, an ineffective initial CTL response can evolve into a persistent antibody-mediated response and, with it, the potential for sustained humoral autoimmunity.This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin.

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CYTOTOXICITY IN GRAFT-VERSUS-HOST REACTION

Cited by 30 publications

References 12 publications

Serum-mediated inhibition of graft-vs.-host reaction.

Serum-mediated inhibition of graft-vs.-host reaction.

Histologic Features of Mycophenolate Mofetil-Related Colitis: A Graft-Versus-Host Disease-Like Pattern

Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity

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