Consequences of double negative regulatory T cell and antigen presenting cell interaction on immune response suppression

McIntyre, Megan S. Ford; Gao, Julia; Li, Xujian; Naeini, Bardya M.; Zhang, Li

doi:10.1016/j.intimp.2010.11.015

Cited by 16 publications

(16 citation statements)

References 42 publications

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“…Fas–FasL interactions have been proposed as the molecular mechanism by which DN T cells eliminate anti-donor T cells, while the elimination of B cells is considered to be perforin-mediated (Zhang et al, 2000, 2006; Priatel et al, 2001; Ma et al, 2008; Ford McIntyre et al, 2011). Interestingly, an accumulation of DN T cells is observed in both Fas- and FasL-deficient mice (Watanabe-Fukunaga et al, 1992; Takahashi et al, 1994), suggesting that the Fas–FasL pathway may regulate the number of DN T cells in vivo .…”

Section: Graft Tolerancementioning

confidence: 99%

“…Indeed, TCR transgenic and non-transgenic DN T cells can also inhibit NK cells (He et al, 2007; Su et al, 2012), B cells (Zhang et al, 2006; Hillhouse et al, 2010; Ford McIntyre et al, 2011), and dendritic cells (Gao et al, 2011). The combination of their distinct phenotypic characteristics and their unique antigen-specific immunoregulatory properties toward multiple cellular targets has prompted investigators to examine the role of DN T cells in various disease models.…”

Section: Introductionmentioning

confidence: 99%

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Immunoregulatory CD4-CD8- T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer

Hillhouse¹,

Delisle²,

Lesage³

2013

Front. Immun.

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A central objective in organ transplantation and the treatment or prevention of autoimmune disease is the achievement of antigen-specific immune tolerance. An additional challenge in bone marrow transplantation for the treatment of hematological malignancies is the prevention of graft-vs-host disease (GVHD) while maintaining graft-vs-tumor activity. Interestingly, CD4-CD8- (double negative, DN) T cells, which exhibit a unique antigen-specific immunoregulatory potential, appear to exhibit all of the properties to respond to these challenges. Herein, we review the therapeutic potential of immunoregulatory DN T cells in various immunopathological settings, including graft tolerance, GVHD, cancer, and autoimmunity.

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Section: Graft Tolerancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunoregulatory CD4-CD8- T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer

Hillhouse¹,

Delisle²,

Lesage³

2013

Front. Immun.

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“…1 T-cell culture and purification 2C F1 DN Tregs and CD8 1 T cells were activated and purified as described previously [31]. The purity and viability of 1B2 were used in various assays.…”

Section: Dn Treg and Cd8mentioning

confidence: 99%

Regulation of antigen‐expressing dendritic cells by double negative regulatory T cells

et al. 2011

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“…Furthermore, DN Tregs are able to suppress B cells and NK cells through the perforin/granzyme pathway for tolerance achievement [31]–[33]. Recently DN Tregs were found to express high levels of CTLA4 which could down regulate CD80/CD86 on mDCs [25].…”

Section: Discussionmentioning

confidence: 99%

“…Recently DN Tregs were found to express high levels of CTLA4 which could down regulate CD80/CD86 on mDCs [25]. DN Tregs could also kill mDCs and activated B cells through the Fas-FasL or the perforin pathway [25], [31]. So far the immune suppression mediated by mouse, rat and human DN Tregs were found to be antigen-specific [17].…”

Section: Discussionmentioning

confidence: 99%

Pretransplant Infusion of Donor B Cells Enhances Donor-Specific Skin Allograft Survival

et al. 2013

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Pretransplant donor lymphocyte infusion (DLI) has been shown to enhance donor-specific allograft survival in rodents, primates and humans. However, the cell subset that is critical for the DLI effect and the mechanisms involved remain elusive. In this study, we monitored donor cell subsets after DLI in a murine MHC class I Ld-mismatched skin transplantation model. We found that donor B cells, but not DCs, are the major surviving donor APCs in recipients following DLI. Infusing donor B, but not non-B, cells resulted in significantly enhanced donor-specific skin allograft survival. Furthermore, mice that had received donor B cells showed higher expression of Ly6A and CD62L on antigen-specific TCRαβ+CD3+CD4−CD8−NK1.1− double negative (DN) regulatory T cells (Tregs). B cells presented alloantigen to DN Tregs and primed their proliferation in an antigen-specific fashion. Importantly, DN Tregs, activated by donor B cells, showed increased cytotoxicity toward anti-donor CD8+ T cells. These data demonstrate that donor B cells can enhance skin allograft survival, at least partially, by increasing recipient DN Treg-mediated killing of anti-donor CD8+ T cells. These findings provide novel insights into the mechanisms underlying DLI-induced transplant tolerance and suggest that DN Tregs have great potential as an antigen-specific immune therapy to enhance allograft survival.

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Consequences of double negative regulatory T cell and antigen presenting cell interaction on immune response suppression

Cited by 16 publications

References 42 publications

Immunoregulatory CD4-CD8- T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer

Immunoregulatory CD4-CD8- T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer

Regulation of antigen‐expressing dendritic cells by double negative regulatory T cells

Pretransplant Infusion of Donor B Cells Enhances Donor-Specific Skin Allograft Survival

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