Clinical Outlook for Type-1 and FOXP3+ T Regulatory Cell-Based Therapy

Gregori, Silvia; Passerini, Laura; Roncarolo, Maria Grazia

doi:10.3389/fimmu.2015.00593

Cited by 49 publications

(43 citation statements)

References 84 publications

(107 reference statements)

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“…Interestingly, recent work shows that ATG directly induces regulatory T cells in vivo [24]. The induction of tolerogenic DC by ATG might be a mechanism supporting the establishment of this T cell population, which is beneficial in the context of aHSCT [31]. The findings described in the current work are focused on the in vitro-analysis of an isolated cell population.…”

Section: Discussionmentioning

confidence: 97%

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Roider

Katzfuß

Matos

et al. 2016

IJMS

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Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon®) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

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Section: Discussionmentioning

confidence: 97%

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Roider

Katzfuß

Matos

et al. 2016

IJMS

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“…Antilymphocyte antibodies might be preferable to induce OT, but the data are non conclusive [42]. Finally, belatacept (antagonist of CD80 and CD86 ligands) could be used [16] to favor tolerance.…”

Section: Treg Generaɵon Treg Expansion and Ac ɵVaɵonmentioning

confidence: 99%

“…By contrast, OT takes place only after several years [7]. OT may rely on Treg, but also probably on B cells, NK/NKT cells, myeloid-derived suppressor cells and tolerogenic dendritic cells [15][16][17][18]. OT is not a definitive status, and rejection may occur after years [3,7].…”

mentioning

confidence: 99%

“…Treg doses reaching 3.5 to 4.5 × 10 6 CD4+CD25+FoxP3+ cells/kg, could then be delivered. This number was estimated to be sufficient to induce OT, from experimental and preliminary studies in autoimmune and GVHD [16,25]. But the optimal human Treg dose is not clearly established, and might be higher than the dose that would be expected from translating murine data.…”

mentioning

confidence: 99%

“…Finally, a last concern is the in vivo fate of infused cells. In the absence of genetic or radioactive labeling it will be difficult to check for their stability, and even more difficult to track them in the allograft or draining lymph nodes [16].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation

Conti

Dahlqvist

Brisson

et al. 2016

Clinics and Research in Hepatology and Gastroenterology

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Targeting Lymphoid Tissues to Promote Immune Tolerance

Chen

Sun

2021

Advanced Therapeutics

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The enormous research progress in autoimmune disorders makes the establishment of long-term clinical tolerance to autoantigens an accessible goal. This strategy endows lymphoid tissues with the tolerogenic ability to induce an unresponsive state toward autoantigens. Lymphoid tissues, as the crossroads, play integral roles in initiating immune activation and immunoregulation. Enormous efforts have driven the exploration of targeting delivery of tolerogenic agents to lymphoid tissues to reverse autoimmune disorders. Herein, the development of various tolerogenic therapies for autoimmune diseases are reviewed, the mechanisms of action from various lymphoid tissues to appropriate cell types by different administration routes are highlighted, and examples of lymphoid tissue-targeting strategies to improve tolerogenic therapy potency are discussed. First lymph nodes-targeting strategies for tolerance induction after interstitial or intra-lymph node (i.LN) injection are summarized, then liver and spleen-mediated tolerance after intravenous administration are described, and finally oral tolerance-based therapies are discussed. It is envisioned that tolerogenic therapy will emerge as a novel treatment for autoimmune diseases.

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Clinical Outlook for Type-1 and FOXP3+ T Regulatory Cell-Based Therapy

Cited by 49 publications

References 84 publications

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

Regulatory T cell therapy: An option to induce operational tolerance in liver transplantation

Targeting Lymphoid Tissues to Promote Immune Tolerance

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