The role of H-2 and Ia antigens in graft-versus-host reactions (GVHR). Presence of host alloantigens on donor cells after GVHR and suppression of GVHR with an anti-Ia antiserum against hose Ia antigens.

Prud’homme, Gérald J.; Sohn, Uik; Delovitch, Terry L.

doi:10.1084/jem.149.1.137

Cited by 34 publications

(21 citation statements)

References 34 publications

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“…A potentiating effect of selective CD80 blockade was again difficult to detect due to the profound elimination of host B cell, even at the reduced donor cell inoculum, and is better seen in the chronic GVHD model. It should be noted that detection of donor T cells by flow cytometry becomes difficult after 2 wk in untreated acute GVHD mice, due to an overall down-modulation of MHC expression (26) and/or acquisition of host MHC by donor cells (27) that parallels disease severity (28). We interpret the reduced numbers of donor CD8 ϩ T cells at 2 wk in anti-CD80 mAb-treated mice (compared with control Ig-treated or untreated acute GVHD) to be a reflection of accelerated GVHD-associated MHC down-regulation rather than impaired engraftment and milder disease.…”

Section: Cd80 And/or Cd86 Blockade In Acute Gvhd Mimics the Effects Smentioning

confidence: 99%

In Vivo CD86 Blockade Inhibits CD4+ T Cell Activation, Whereas CD80 Blockade Potentiates CD8+ T Cell Activation and CTL Effector Function

Lang

Nguyen

Peach

et al. 2002

The Journal of Immunology

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To address whether a functional dichotomy exists between CD80 and CD86 in naive T cell activation in vivo, we administered anti-CD80 or CD86 blocking mAb alone or in combination to mice with parent-into-F1 graft-vs-host disease (GVHD). In this model, the injection of naive parental T cells into unirradiated F1 mice results in either a Th1 cytokine-driven, cell-mediated immune response (acute GVHD) or a Th2 cytokine-driven, Ab-mediated response (chronic GVHD) in the same F1 recipient. Combined CD80/CD86 blockade beginning at the time of donor cell transfer mimicked previous results seen with CTLA4Ig and completely abrogated either acute or chronic GVHD by preventing the activation and maturation of donor CD4+ T cells as measured by a block in acquisition of memory marker phenotype and cytokine production. Similar results were seen with selective CD86 blockade; however, the degree of CD4 inhibition was always less than that seen with combined CD80/CD86 blockade. A more striking effect was seen with selective CD80 blockade in that chronic GVHD was converted to acute GVHD. This effect was associated with the induction of Th1 cytokine production, donor CD8+ T cell activation, and development of antihost CTL. The similarity of this effect to that reported for selective CTLA4 blockade suggests that CD80 is a critical ligand for CTLA4 in mediating the down-regulation of Th1 responses and CD8+ T cell activation. In contrast, CD86 is critical for the activation of naive CD4+ T cells in either a Th1 or a Th2 cytokine-mediated response.

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Section: Cd80 And/or Cd86 Blockade In Acute Gvhd Mimics the Effects Smentioning

confidence: 99%

In Vivo CD86 Blockade Inhibits CD4+ T Cell Activation, Whereas CD80 Blockade Potentiates CD8+ T Cell Activation and CTL Effector Function

Lang

Nguyen

Peach

et al. 2002

The Journal of Immunology

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“…it is interesting to speculate that antigen transfer could be a biologically important mechanism for cell communication. It was recently reported that antigen transfer plays a role in the graft-versus-host-reaction (GvH) [12]. Preud'homme et al [12] found host alloantigens on donor cells after GvH.…”

Section: Resultsmentioning

confidence: 99%

“…It was recently reported that antigen transfer plays a role in the graft-versus-host-reaction (GvH) [12]. Preud'homme et al [12] found host alloantigens on donor cells after GvH. These alloantigens were H-2K, H-2D, and la, and it was possible to suppress the GvH by daily injections of anti-la sera.…”

Section: Resultsmentioning

confidence: 99%

Priming against Stimulator‐derived Alloantigens Bound onto MLC‐activated Blasts

Gänsbacher¹,

Zier²,

Albert³

1980

Scand J Immunol

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Several investigators have reported that antigen transfer between stimulator and responder cells occurs. We investigated whether it was possible to prime against such stimulator-derived alloantigens bound onto mixed lymphocyte culture (MLC)-activated blasts. For this purpose we generated blasts bearing bound stimulator-derived alloantigens in a primary MLC. Subsequently we primed a new family member against these blasts and after 10 days restimulated with all family members. Our results showed that it was indeed possible to sensitize against this transferred antigen and to obtain specific restimulation. Moreover we demonstrated that it was possible to abolish this specific response by treating these blast cells with trypsin.

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“…Furthermore, induction of the antitumor activity was abolished by administration of anti I-A a antibody, which caused a decline in Ia-positive macrophages in the peritoneal cavity, at the time of tumor antigen injection. In studies by others, in vivo administration of anti-Ia antibody was shown to cause inhibition of delayed type-hypersensitivity to a tumor-specific antigen [20], antibody production [25,26], and graftversus-host reactions [21]. However the relationship be-220 tween inhibition of these responses and Ia-positive cells was not clear.…”

Section: Discussionmentioning

confidence: 96%

Correlation between increase in Ia-bearing macrophages and induction of T cell-dependent antitumor activity by Lactobacillus casei in mice

Kato

Yokokura

Mutai

1988

Cancer Immunol Immunother

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When Lactobacillus casei YIT 9018 (LC 9018) or Corynebacterium parvum, known to be immunomodulators possessing antitumor activity, were injected i.p. into BALB/c mice, peritoneal exudate macrophage Ia antigen detected by indirect immunofluorescence method was expressed on their cell surface, but it was not expressed following the injection of 10% proteose peptone, an inflammatory agent, or Lactobacillus fermentum YIT 0159 (LF 0159), which have no antitumor activity. The percentage and absolute number of Ia-positive peritoneal macrophages were maximum on the 7th day after the injection of LC 9018. Immunization by injection of Meth A fibrosarcoma cells treated with mitomycin C (MMC-Meth A) 7 days after LC 9018 injection suppressed the growth of Meth A implanted i.p. 14 days after MMC-Meth A injection. A shorter interval between the injections of LC 9018 and MMC-Meth A did not allow suppression of Meth A growth. These results showed that the increase in Ia-positive macrophages in the peritoneal cavity coincided with the effective interval for induction of the antitumor activity by LC 9018. The antitumor activity induced by injections of LC 9018 and MMC-Meth A did not affect the growth of RL male 1 leukemic cells, syngeneic to BALB/c mice. Neutralization (Winn type) tests showed that peritoneal T lymphocytes possessed tumor cytotoxicity and that the antitumor capacity was reduced by in vivo treatment with anti I-Ad monoclonal antibody simultaneously with and 1 day prior to MMC-Meth A injection. These results indicate that LC 9018-induced Ia-positive macrophages, which first encounter a tumor antigen in the peritoneal cavity, play an important role in the in vivo induction of tumor specific T cell-mediated antitumor immunity.

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The role of H-2 and Ia antigens in graft-versus-host reactions (GVHR). Presence of host alloantigens on donor cells after GVHR and suppression of GVHR with an anti-Ia antiserum against hose Ia antigens.

Cited by 34 publications

References 34 publications

In Vivo CD86 Blockade Inhibits CD4+ T Cell Activation, Whereas CD80 Blockade Potentiates CD8+ T Cell Activation and CTL Effector Function

In Vivo CD86 Blockade Inhibits CD4+ T Cell Activation, Whereas CD80 Blockade Potentiates CD8+ T Cell Activation and CTL Effector Function

Priming against Stimulator‐derived Alloantigens Bound onto MLC‐activated Blasts

Correlation between increase in Ia-bearing macrophages and induction of T cell-dependent antitumor activity by Lactobacillus casei in mice

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