The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts.

Hall, Bruce M.; Dorsch, Susan E.; Roser, Bruce

doi:10.1084/jem.148.4.878

Cited by 113 publications

(90 citation statements)

References 33 publications

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“…Glomeruli were stained with MRCOx-12, which recognizes rat Ig -L chains (34), C9 polyclonal rabbit anti-rat Ab (35) (a kind gift of S. Piddlesden, The Austin Research Institute, Heidelberg, Victoria, Australia), and goat anti-rat C3 peroxidase conjugate (Nordik Immunology, Tilberg, The Netherlands). (41) (all purchased from PharMingen). Cellular infiltrates were counted, with labels covered, under ϫ40 magnification, and results were expressed as the mean Ϯ SD of cells per high power field or glomerulus, as described (17).…”

Section: Immunoperoxidase Cytochemistry Of Renal Cortex and Isolated mentioning

confidence: 99%

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IL-4 Therapy Prevents the Development of Proteinuria in Active Heymann Nephritis by Inhibition of Tc1 Cells

Spicer

Boyd

et al. 2001

The Journal of Immunology

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The role of IL-4, a key Th2 cytokine, in promoting or inhibiting active Heymann nephritis (HN) was examined. HN is induced by immunization with Fx1A in CFA, and proteinuria in HN is associated with subepithelial IgG and C3 deposition and infiltration of CD8+ T-cytotoxic 1 (Tc1) cells and macrophages into glomeruli, as well as induction of Abs to Crry. Treatment with rIL-4 from the time of Fx1A/CFA immunization stimulated an earlier IgG1 response to Fx1A, induced anti-Crry Abs, and up-regulated IL-4 mRNA in lymphoid tissue, but did not alter proteinuria. Treatment with MRCOx-81, an IL-4-blocking mAb, resulted in greater proteinuria, which suggests endogenous IL-4 regulated the autoimmune response. Delay of rIL-4 treatment until 4 wk post-Fx1A/CFA immunization and just before the onset of proteinuria prevented the development of proteinuria and reduced Tc1 cell infiltrate in glomeruli. Delayed treatment with IL-4 had no effect on titer or isotype of Abs to Fx1A or on Ig, C3, and C9 accumulation in glomeruli. Treatment with rIL-13, a cytokine that alters macrophage function such as rIL-4, but has no direct effect on T or B cell function, reduced glomerular macrophage infiltrate, but did not prevent proteinuria or CD8+ T cell infiltrate. Anti-Crry Abs were paradoxically only induced with rIL-4 therapy, not in HN controls with proteinuria. It was concluded that the rIL-4 effect was probably by inhibition of Tc1 cells, which normally mediate the glomerular injury that results in proteinuria.

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Section: Immunoperoxidase Cytochemistry Of Renal Cortex and Isolated mentioning

confidence: 99%

“…, and B cells (MRCOx-33 ϩ /G4.18 Ϫ ) before they were analyzed on FACScan (BD Biosciences, San Jose, CA), as described (41).…”

Section: Staining Of Lymph Node Cell Subpopulationsmentioning

confidence: 99%

IL-4 Therapy Prevents the Development of Proteinuria in Active Heymann Nephritis by Inhibition of Tc1 Cells

Spicer

Boyd

et al. 2001

The Journal of Immunology

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“…C D4 ϩ T cells are the major initiating cells of the cognate immune response in rejection (1)(2)(3). CD4 ϩ T cells alone are capable of rejecting allografts (4).…”

mentioning

confidence: 99%

“Pruning” of Alloreactive CD4+ T Cells Using 5- (and 6-)Carboxyfluorescein Diacetate Succinimidyl Ester Prolongs Skin Allograft Survival

Watson

Zhang

Sartor

et al. 2004

The Journal of Immunology

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Removal of alloreactive cells by either thymic deletion or deletion/anergy in the periphery is regarded as crucial to the development of tolerance. Dyes, such as CFSE, that allow monitoring of cell division suggest that in vitro proliferation could be a used as a way of “pruning” alloreactive cells while retaining a normal immune repertoire with retention of memory to previously encountered pathogens. This would overcome the problems occurring as a result of therapies that use massive depletion of T cells to allow acceptance of organ transplants or bone marrow grafts. We therefore used a skin graft model of CD4-mediated T cell rejection across a major H-2 mismatch (C57BL/6 (H-2b) to BALB/c (H-2d) mice) to evaluate whether nondividing CD4+ T cells derived from a mixed lymphocyte culture would exhibit tolerance to a skin graft from the initial stimulator strain. We demonstrate that selective removal of dividing alloreactive CD4+ T cells resulted in marked specific prolongation of allogeneic skin graft survival, and that the nondividing CD4+ T cells retained a broad TCR repertoire and the ability to maintain memory. This novel way of depleting alloreactive T cells may serve as a useful strategy in combination with other mechanisms to achieve transplant tolerance.

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“…While T cell mediated immunity is central in allogeneic rejection mechanisms, humoral or antibody mediated immune responses are also involved [107][108]. Since the early reports outlining the capacity of MSCs to inhibit T cell proliferation in vitro, the field has progressed rapidly and we now have a greater understanding of how MSCs mediate their effects.…”

Section: Interactions Between Mscs and The Adaptive Immune Responsementioning

confidence: 99%

“…In addition, innate immunity is also triggered by danger signals. Although rejection of allogeneic grafts is known to be mediated primarily by T cell and antibody responses [107,108], a number of studies now suggest that the innate immune response plays a role in the immune response to solid organ transplantation (reviewed in [109]). …”

Section: Influence Of Msc On the Innate Immune Responsementioning

confidence: 99%

Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation

English¹,

Mahon²,

Wood³

2013

CDD

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Mesenchymal stromal cells (MSCs) participate in repair of damaged tissues, possess the potential to serve as a useful tool in the drug discovery field and exert immunosuppressive effects as demonstrated by their ability to modulate the immune response. Herein, the roles played by MSC differentiation and/or production of trophic factors involved in tissue repair are discussed. MSCs offer the opportunity to probe targets that conventional or differentiated cell lines do not express; thus providing a more refined system that allows identification of novel therapeutics. However, there are difficulties associated with drug discovery assays to which MSCs are not exempt. The immunosuppressive potential of MSCs has already been utilised in clinical trials where MSCs have been used to treat patients with graft-versus-host disease (GvHD) and autoimmune diseases. Another possible therapeutic application of MSCs lies in the field of transplantation tolerance. Although the capacity of MSCs to modulate immune responses has received much attention, the role of MSCs in transplantation tolerance is as yet unclear. In this review, we discuss the evidence for MSC induction of a state of tolerance in the transplantation setting.

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The cellular basis of allograft rejection in vivo. I. The cellular requirements for first-set rejection of heart grafts.

Cited by 113 publications

References 33 publications

IL-4 Therapy Prevents the Development of Proteinuria in Active Heymann Nephritis by Inhibition of Tc1 Cells

IL-4 Therapy Prevents the Development of Proteinuria in Active Heymann Nephritis by Inhibition of Tc1 Cells

“Pruning” of Alloreactive CD4+ T Cells Using 5- (and 6-)Carboxyfluorescein Diacetate Succinimidyl Ester Prolongs Skin Allograft Survival

Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation

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