Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: Is now the right time?

Jethwa, Hannah; Adami, Antonella; Maher, John

doi:10.1016/j.clim.2013.11.004

Cited by 54 publications

(39 citation statements)

References 112 publications

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“…A number of clinical trials have demonstrated that injecting Tregs following haploidentical hematopoietic stem cell transplantation can provide durable immune tolerance [39]. In addition, several studies demonstrated that FoxP3 + Tregs and allo-specific type 1 regulatory (Tr1) cells prevent graft-versus-host disease (GvHD) without inhibiting immune reconstitution [40][41][42][43][44].…”

Section: Treg Dysfunction and Effector/treg Imbalance In Autoimmune Dmentioning

confidence: 99%

GITR+ regulatory T cells in the treatment of autoimmune diseases

Petrillo

Ronchetti

Alunno

et al. 2015

Autoimmunity Reviews

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Section: Treg Dysfunction and Effector/treg Imbalance In Autoimmune Dmentioning

confidence: 99%

GITR+ regulatory T cells in the treatment of autoimmune diseases

Petrillo

Ronchetti

Alunno

et al. 2015

Autoimmunity Reviews

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“…[12][13][14][15] In contrast to polyclonal Tregs, antigen-specific Tregs can recognize the disease-associated antigen and exert their suppressive action at sites of inflammation, eg, islets of Langerhans or the central nervous system. 16,17 Recently, the generation of antigenspecific human Tregs via viral transduction of a tumor-associated antigen-specific TCR was reported. 9,11,18 These results indicated that transduction of specific TCR could render Tregs antigen specific (monoclonal) and able to suppress immune responses to specific antigens.…”

Section: Introductionmentioning

confidence: 99%

Engineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses

Kim

Zhang

et al. 2015

Blood

137

154

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Expansion of human regulatory T cells (Tregs) for clinical applications offers great promise for the treatment of undesirable immune responses in autoimmunity, transplantation, allergy, and antidrug antibody responses, including inhibitor responses in hemophilia A patients. However, polyclonal Tregs are nonspecific and therefore could potentially cause global immunosuppression. To avoid this undesirable outcome, the generation of antigen-specific Tregs would be advantageous. Herein, we report the production and properties of engineered antigen-specific Tregs, created by transduction of a recombinant T-cell receptor obtained from a hemophilia A subject's T-cell clone, into expanded human FoxP3(+) Tregs. Such engineered factor VIII (FVIII)-specific Tregs efficiently suppressed the proliferation and cytokine production of FVIII-specific T-effector cells. Moreover, studies with an HLA-transgenic, FVIII-deficient mouse model demonstrated that antibody production from FVIII-primed spleen cells in vitro were profoundly inhibited in the presence of these FVIII-specific Tregs, suggesting potential utility to treat anti-FVIII inhibitory antibody formation in hemophilia A patients.

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“…32,33 Several animals studies support that CAR-expressing Tregs can be efficacious in preventing experimental autoimmune encephalitis (EAE) 34 or murine colitis and its associated cancer 35 or may be in the future will support the efficacy of CARexpressing Tregs in the setting of transplantation. According to in vivo expansion of nTregs, many variety of strategies used to induce Treg number or potency in vivo including expansion of nTregs and conversion of non-Tregs to iTregs like, prevention of allograft rejection in mice by treating mice prior to allografting with a donor alloantigen and a non-depleting anti-CD4 antibody which achieves Treg expansion.…”

Section: Induction or Engineer Of Tregs Cell Ex Vivo And In Vivomentioning

confidence: 99%