In vivo and in vitro production of IFN-beta and IFN-gamma during graft vs host disease.

Cleveland, Mark; Annable, C R; Klimpel, Gary R.

doi:10.4049/jimmunol.141.10.3349

Cited by 35 publications

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“…Increased numbers of la + KC have been noted in vivo in the setting of graft-versus-host disease (GVHD) (33). The infiltrating lymphocyte populations in the liver and spleen are the known sources of 'YlFN release during this reaction (34). However, the increased percentage of KC expression of lad antigen in several groups of mice post-BMT is unlikely to be related to GVHD-induced 'YlFN induction.…”

Section: Discussionmentioning

confidence: 99%

Kupffer Cell Engraftment Across the Major Histocompatibility Barrier in Mice

Paradis,

Sharp,

Vallera

et al. 1990

J. pediatr. gastroenterol. nutr.

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The source of population renewal for Kupffer cells (KC), the major antigen‐presenting cells of the liver, remains controversial. Using a well‐described murine bone marrow transplantation (BMT) model in which the donor and recipient are disparate at the major histocompatibility complex (MHC), we have studied (a) the source of KC renewal by genotypic analysis, cell surface (class II or la) antigens, and immune function assays; (b) the level of KC la expression post‐BMT in transplant recipients: and (c) the capacity of newly repopulating KC to present antigen to an la‐restricted T cell clone of donor la type. Kupffer cell engraftment, as assessed by each of these three methods, was noted to be predominantly of donor marrow origin by day 21 post‐BMT. Cell surface la expression was comparable to that of nontransplanted controls of the same strain as donor mice. Within 7 days post‐BMT, KC were mature antigen‐presenting cells. We conclude that KC rapidly repopulate the liver from donor bone marrow post‐BMT, and these macrophages are able to interact with T lymphocytes in an immunocompetent manner.

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Section: Discussionmentioning

confidence: 99%

Kupffer Cell Engraftment Across the Major Histocompatibility Barrier in Mice

Paradis,

Sharp,

Vallera

et al. 1990

J. pediatr. gastroenterol. nutr.

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Interferon-gamma gene expression during acute graft-versus-host disease: relationship to MHC induction and tissue injury

et al. 1999

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The pathogenetic role of interferon‐γ (IFN‐γ) in acute graft‐versus‐host disease (GVHD) was examined in a murine model. IFN‐γ gene expression was evaluated by northern blotting and mRNA in situ hybridization. The temporal and tissue specific patterns of IFN‐γ gene expression were related to the patterns of major histocompatibility complex (MHC) antigen induction and of tissue injury. Markedly increased levels of IFN‐γ transcripts were seen in the spleen during the early lymphoproliferative phase and coincided with widespread MHC induction in non‐lymphoid tissues. Increased IFN‐γ transcripts were also found in the non‐lymphoid target tissues during the phase of subsequent tissue injury. These findings support a role for IFN‐γ in leading to widespread MHC induction during acute GVHD and suggest that IFN‐γ may also contribute to target tissue injury during acute GVHD. Copyright © 1999 John Wiley & Sons, Ltd.

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Role of antigen‐presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages

Duncan

Swain

1994

Eur J Immunol

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Immune challenges can elicit polarized responses skewed towards the development of T helper type 1 (Th1) or Th2 T cell subsets. To determine if distinct antigen-presenting cells (APC) populations might selectively influence Th subset development, we studied the role of two key APC populations, B cells and macrophages, in the differentiation of effector Th populations from naive precursor Th in vitro. Antigen (Ag)-specific, naive CD4+ T cells were enriched from a mouse strain, AND, bearing a transgenic alpha/beta T cell receptor (TCR) encoding reactivity with pigeon cytochrome c peptide 88-104. Peptide Ag was used throughout these studies so that differences in the uptake and processing by the two APC populations would not influence the results. Both APC populations, activated B cells and bone marrow-derived macrophages, supported the development of effector Th having the capacity to secrete high levels of cytokines when restimulated. Regardless of APC population present during effector development, exogenous interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) had dominant effects on Th subset development. Thus, with both APC populations, effector Th generated in the presence of IFN-gamma acquired a Th1-type cytokine profile, Th generated with IL-4 acquired a Th2-type cytokine profile, and Th generated without IFN-gamma or IL-4 acquired a Th0-type cytokine profile. B cells and macrophages also had equivalent APC function in the restimulation of Th1 and Th2-like effectors, since only minor differences in cytokine production were noted for these effector populations when restimulated with the two APC populations. However, in 8 of 19 experiments, the Th0-like effector population generated in the presence of IL-2 differentially responded to restimulation with B cells and macrophages, secreting significantly more IFN-gamma when restimulated with B cells, and significantly more IL-4 when restimulated with macrophages. We also found that Th effector populations recultured in IFN-gamma or IL-4 assumed a more Th1 or Th2-like phenotype, respectively, regardless of their initial cytokine profile. We conclude that through a subtle capacity to skew cytokine production by a Th0 subset, different APC may selectively influence Th subset development under conditions of prolonged or chronic stimulation in an autocrine fashion.

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In vivo and in vitro production of IFN-beta and IFN-gamma during graft vs host disease.

Cited by 35 publications

References 0 publications

Kupffer Cell Engraftment Across the Major Histocompatibility Barrier in Mice

Kupffer Cell Engraftment Across the Major Histocompatibility Barrier in Mice

Interferon-gamma gene expression during acute graft-versus-host disease: relationship to MHC induction and tissue injury

Role of antigen‐presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages

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