Enhancement of cyclosporin A-induced autologous graft-versus-host disease after peripheral blood stem cell transplantation by utilizing selected CD34+ cells

Miura, Yuji; Ueda, Mikio; Takami, Akiyoshi; Shiobara, Shintaro; Nakao, Shinji; Hess, A. D.

doi:10.1038/sj.bmt.1704208

Cited by 5 publications

(6 citation statements)

References 38 publications

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“…Nonetheless, autologous transplants offer much hope with respect to targeting tumors; autoaggression elicited by these transplants can serve as anti--cancer therapy [36]. In autologous transplants, cyclosporin A represses the effects of autoreactive T cells and inhibits the reconstitution of the immune system [32,36]. Furthermore, it has been shown that autoreactive CD8 + T cells from autologous transplants can target breast cancer cells, myelomas, and lymphomas [36].…”

Section: Autologous Transplantsmentioning

confidence: 99%

“…In autologous transplants, cyclosporin A represses the effects of autoreactive T cells and inhibits the reconstitution of the immune system [32,36]. Furthermore, it has been shown that autoreactive CD8 + T cells from autologous transplants can target breast cancer cells, myelomas, and lymphomas [36]. The benefit of such transplants is a decrease in the relapse rate of hematological malignancies in patients with GVHD, suggesting the therapeutic benefits of such treatments [36].…”

Section: Autologous Transplantsmentioning

confidence: 99%

“…For example, MSC-mediated immunosuppression may have potential therapeutic uses in the treatment of autoimmune diseases, whereas MSC-mediated immunostimulation can potentially limit the spread of cancer. The exploitation of IL-10 and IDO in promoting transplant tolerance can offer a critical therapeutic strategy in allogeneic and autologous grafts, whereas cyclosporin A-induced GVHD in autologous transplants suggests an avenue for targeting tumor cells, including malignancies of the breast and BM [36]. The evidence that MHC-II expression on certain MSCs can stimulate a mild allogeneic response may offer potential in targeting cancer cells as well.…”

Section: Future Potential Of Mscsmentioning

confidence: 99%

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Immunological properties of mesenchymal stem cells and clinical implications

Patel

Sherman

Munoz

et al. 2008

Arch. Immunol. Ther. Exp.

145

101

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The rapid evolution of experimental data has acknowledged the critical relevance of immune biology in stem cell research. It appears that efficient transfer of stem cells to patients requires robust analyses of the immune properties as well as the responses of the stem cells to immune mediators. This review discusses the biology of adult human mesenchymal stem cells (MSCs) in the context of immunology. MSCs are pluripotent, self-renewing cells with the potential for tissue regeneration, for example the repair of bone, cartilage, tendon, ligament, skeletal muscle, and cardiac muscle. MSCs have also been shown to transdifferentiate into cells of ectodermal origin, such as neurons. MSCs are located in perfused areas of adult bone marrow, whereas hematopoietic stem cells are located in poorly perfused areas of the same organ. MSCs show bimodal, i.e. anti-inflammatory and immune-enhancing, immune responses. MSCs also regulate immune responses such as the regulation of antibody production by B cells, alterations in T cell subtypes, and immune tolerance of allogeneic transplants. MSCs also have the potential for gene delivery. This review explores the diverse clinical potential for MSCs and discusses the limitations and advantages of their immunomodulatory properties.

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Section: Autologous Transplantsmentioning

confidence: 99%

Section: Autologous Transplantsmentioning

confidence: 99%

Section: Future Potential Of Mscsmentioning

confidence: 99%

See 1 more Smart Citation

Immunological properties of mesenchymal stem cells and clinical implications

Patel

Sherman

Munoz

et al. 2008

Arch. Immunol. Ther. Exp.

145

101

View full text Add to dashboard Cite

show abstract

“…10,14,19,21,22,24,26 Auto-GVHD generally appears within the first several weeks after auto-HCT, typically manifesting as a localized or more generalized erythematous maculopapular rash involving the face, trunk, extremities, palms and soles. The histopathologic appearance is inseparable from classic acute GVHD and rarely is greater than grade II in appearance.…”

Section: Incidence and Clinical Characteristicsmentioning

confidence: 99%

“…While CsA clearly is important in the pathogenesis of auto-GVHD, others have suggested that the depletion of regulatory T cells (Tregs) which occurs after the preparative chemotherapy, in addition, may inhibit peripheral tolerance and contribute to the development of auto-GVHD. 19,20 Thus, it appears that auto-GVHD may arise as a result of impaired immune tolerance, both central through treatment with CsA and peripheral through Treg cell depletion.…”

Section: Introductionmentioning

confidence: 99%

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Kline

Subbiah

Lazarus

et al. 2007

Bone Marrow Transplant

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Cytolytic effector mechanisms and gene expression in autologous graft-versus-host disease: distinct roles of perforin and Fas ligand

Miura¹,

Thoburn²,

Bright³

et al. 2004

Biology of Blood and Marrow Transplantation

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The administration of cyclosporin A (CsA) after autologous stem cell transplantation (SCT) paradoxically elicits a systemic autoimmune syndrome that resembles graft-versus-host disease (GVHD); this is termed autologous GVHD (autoGVHD). Although dominated by activated CD8+ cytotoxic T lymphocytes, the complex cellular reaction also includes CD4+ T cells and involves multiple effector mechanisms. To determine the temporal development and relative importance of these mechanisms in autoGVHD, perforin/granzyme, Fas ligand (FasL), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF)-alpha, and interleukin-18 gene expression in peripheral blood mononuclear cells was examined in 36 patients treated with CsA after SCT. Quantitative real-time polymerase chain reaction analysis revealed that perforin/granzyme B, TNF-alpha, and interleukin-18 messenger RNA (mRNA) levels in peripheral blood mononuclear cells from patients in whom autoGVHD developed were markedly higher (and temporally associated with the onset of autoaggression) compared with the levels detected in healthy individuals and in control, non-CsA-treated SCT patients. It is interesting to note that patients in whom autoGVHD did not develop also demonstrated increased mRNA levels for these cytokines: however, expression was substantially lower compared with that in patients with autoGVHD. It is important to note that IFN-gamma mRNA levels were selectively increased in CD8+ cells only from patients in whom autoGVHD developed. The development of autocytolytic T cells in autoGVHD correlated with increased expression of perforin, IFN-gamma, and TNF-alpha mRNA. Furthermore, enhanced autoreactive T-cell activity and the induction of autoGVHD was also concordant with perforin and TNF-alpha mRNA upregulation in CD4+ cells. Surprisingly, FasL mRNA levels were significantly decreased, with a progressive loss of FasL mRNA expression as autocytolytic activity increased. These findings suggest that IFN-gamma/perforin-based CD8+ cytotoxic T lymphocytes seem to play a dominant role in autoGVHD and that TNF-alpha/perforin-based CD4+ cells may amplify this autoaggressive syndrome. The FasL pathway may play an important role in the regulation of this immune syndrome.

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Enhancement of cyclosporin A-induced autologous graft-versus-host disease after peripheral blood stem cell transplantation by utilizing selected CD34+ cells

Cited by 5 publications

References 38 publications

Immunological properties of mesenchymal stem cells and clinical implications

Immunological properties of mesenchymal stem cells and clinical implications

Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance

Cytolytic effector mechanisms and gene expression in autologous graft-versus-host disease: distinct roles of perforin and Fas ligand

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