Cutaneous T cell lymphoma and graft-versus-host disease: A comparison of in vivo effects of extracorporeal photochemotherapy on Foxp3+ regulatory T cells

Rao, Vidar; Saunes, Marit; Jørstad, Størker; Moen, Torolf

doi:10.1016/j.clim.2009.08.016

Cited by 33 publications

(28 citation statements)

References 52 publications

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“…Donor Tregs were important to reverse established GVHD in a murine model and Tregs were found to be increased in patients with acute and chronic GVHD when successfully treated with ECP. 30,45,46 In contrast to these studies, we observed a significant increase of host-type Tregs while leaving donor Tregs unaffected in ECP-treated mice. More importantly, these ECP-induced Tregs had significantly higher surface expression of the suppressor molecule CTLA4, potentiating their suppressive capacity.…”

Section: Discussioncontrasting

confidence: 99%

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

Florek

Sega

Leveson-Gower

et al. 2014

Blood

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Key Points• Prophylactic ECP protects against GVHD in a murine BMT model.• ECP provides apoptotic signals that promote tolerance through dendritic cells and Tregs.Acute graft-versus-host disease (GVHD) is induced by alloreactivity of donor T cells toward host antigens presented on antigen-presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (P < .0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased nuclear factor-kB engagement, increased regulatory T-cell (Treg) numbers with enhanced expression of cytolytic T lymphocyte-associated antigen 4, potentiating their suppressive function. The protective effect required host production of interleukin-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by cotreatment with lipopolysaccharide, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting. (Blood.

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Section: Discussioncontrasting

confidence: 99%

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

Florek

Sega

Leveson-Gower

et al. 2014

Blood

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“…We found that Foxp3 mRNA expression levels were not increased in lesional skin of CTCL (data not shown), which was consistent with a previous report (43). In another report, however, the relative amount of Tregs in peripheral blood was higher in CTCL compared with healthy controls (44). In another study, dysfunction of peripheral Tregs in certain CTCL patients was reported, although the frequency of Tregs did not differ significantly between patients and controls (45).…”

Section: Discussionsupporting

confidence: 91%

IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma

Miyagaki

Sugaya

Suga

et al. 2011

Clinical Cancer Research

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Purpose: Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, T H 2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22-producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of T H 22-and T H 17-related molecules in lesional skin and sera isolated from patients with CTCL.Experimental Design: Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry.Results: IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity.Conclusions: Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6 þ cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL. Clin Cancer Res; 17(24); 7529-38. Ó2011 AACR.

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“…Extending pre-clinical findings to humans, Lamioni et al observed that ECP treatments promote a significant increase in regulatory T cells in the blood of cardiac and lung transplant patients compared to untreated healthy individuals and patients who received traditional immunosuppressants (125). Treg function in both GVHD and CTCL patients was reported to be strengthened as a result of ECP treatments (135). The frequency of circulating CD4+CD25+GITR+CD62L+Foxp3+ Tregs with suppressive function increased in GVHD patients treated with ECP, suggesting an association between elevation in Tregs and response to ECP treatments (136).…”

Section: Apoptotic Cell Infusion Leads To the Generation Of Regulatormentioning

confidence: 97%

Steady-State Cell Apoptosis and Immune Tolerance - Induction of Tolerance Using Apoptotic Cells in Type 1 Diabetes and Other Immune-Mediated Disorders

Xia¹,

Campbell²,

Benjamin³

et al. 2011

Type 1 Diabetes - Pathogenesis, Genetics and Immunotherapy

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Cutaneous T cell lymphoma and graft-versus-host disease: A comparison of in vivo effects of extracorporeal photochemotherapy on Foxp3+ regulatory T cells

Cited by 33 publications

References 52 publications

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma

Steady-State Cell Apoptosis and Immune Tolerance - Induction of Tolerance Using Apoptotic Cells in Type 1 Diabetes and Other Immune-Mediated Disorders

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