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

Gao, Julia; McIntyre, Megan S. Ford; Juvet, S.; Diao, Jun; Li, Xujian; Vanama, Ramesh; Mak, Tak W.; Cattral, Mark S.; Zhang, Li

doi:10.1002/eji.201141428

Cited by 48 publications

(58 citation statements)

References 32 publications

(35 reference statements)

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“…Subsequent studies reported that DN Tregs displayed antigen specific suppressive activity both in vitro and in vivo (51). DN Tregs not only suppress CD8+ T cell responses, but also inhibit CD4+ T cells (57), B cells (58), NK cells (59), and dendritic cells (DC) (60). …”

Section: Tcrαβ+ Cd4-cd8- Double Negative Tregs (Dn Treg)mentioning

confidence: 99%

“…There is also evidence that murine DN Tregs regulate immune responses at the level of antigen presenting dendritic cells (DC). Gao and co-workers (60) demonstrated that murine DN Tregs expressed high levels of CTLA-4 and down-regulated costimulatory molecules CD80 and CD86 on antigen-presenting mature DCs. Moreover, DN Tregs killed syngeneic antigen-loaded DCs or allogeneic DCs through a Fas-FasL pathway.…”

Section: Tcrαβ+ Cd4-cd8- Double Negative Tregs (Dn Treg)mentioning

confidence: 99%

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Advances on Non-CD4 + Foxp3+ T Regulatory Cells

Ligocki

Niederkorn

2015

Transplantation

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The overwhelming body of research on T regulatory cells (Tregs) has focused on CD4+CD25+Foxp3+ T cells. However, recent years have witnessed a resurgence in interest in CD4-CD8+, CD4-CD8- (double negative; DN), and CD4+Foxp3- Tr1 Tregs and their role in controlling autoimmune diseases and in promoting the survival of organ allografts and xenografts. CD8+ and DN Tregs can arise spontaneously (natural Tregs) or can be induced in situ. Both CD8+ and DN Tregs have been shown to enhance the survival of organ allografts and xenografts. Additionally, both can suppress alloimmune responses by contact-dependent mechanisms by either inducing apoptosis or mediating direct cytolysis of effector T cells. CD8+, DN, and Tr1 Tregs can also act in a contact-independent manner by elaborating soluble immunosuppressive factors such TGF-β and IL-10. Applying CD8+, DN, and Tr1 Tregs for enhancing the survival of organ allografts and xenografts is still in its infancy but holds significant potential. Furthermore, there is a need for a more comprehensive understanding of how current immunosuppressive therapies applied to organ transplantations affect the wide array of Treg populations.

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Section: Tcrαβ+ Cd4-cd8- Double Negative Tregs (Dn Treg)mentioning

confidence: 99%

Section: Tcrαβ+ Cd4-cd8- Double Negative Tregs (Dn Treg)mentioning

confidence: 99%

Advances on Non-CD4 + Foxp3+ T Regulatory Cells

Ligocki

Niederkorn

2015

Transplantation

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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]. DN Tregs could also kill mDCs and activated B cells through the Fas-FasL or the perforin pathway [25], [31].…”

Section: Discussionmentioning

confidence: 99%

“…Cultures were found to be greater than 90% CD19 + . BM derived mature DCs (mDCs) were obtained as previously described [25]. On day 8–9, non-adherent cells were collected and used as iDCs.…”

Section: Methodsmentioning

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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“…Trogocytosis is mediated with CD28, CTLA-4, and programmed death ligand 1 (PDL-1) and involves CD80/CD86 removal from the surface of DCs therefore increasing the inhibitory capacity of Tregs. Tregs from the CTLA-4-knockdown mice failed to suppress CD80/CD86 production suggesting for a key role of CTLA-4 in the suppression of CD80/CD86 expression in antigen-presenting mature DCs (Gao et al, 2011). CTLA-4 binding to CD80/CD86 on the surface of DCs has a major role in inducing tolerance (Oderup et al, 2006).…”

Section: Crosstalks Between Dcs and Tregs In Atherosclerosismentioning

confidence: 99%

Dendritic cells in atherosclerotic inflammation: the complexity of functions and the peculiarities of pathophysiological effects

et al. 2014

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Atherosclerosis is considered as a chronic disease of arterial wall, with a strong contribution of inflammation. Dendritic cells (DCs) play a crucial role in the initiation of proatherogenic inflammatory response. Mature DCs present self-antigens thereby supporting differentiation of naïve T cells to effector cells that further propagate atherosclerotic inflammation. Regulatory T cells (Tregs) can suppress proinflammatory function of mature DCs. In contrast, immature DCs are able to induce Tregs and prevent differentiation of naïve T cells to proinflammatory effector T cells by initiating apoptosis and anergy in naïve T cells. Indeed, immature DCs showed tolerogenic and anti-inflammatory properties. Thus, DCs play a double role in atherosclerosis: mature DCs are proatherogenic while immature DCs appear to be anti-atherogenic. Tolerogenic and anti-inflammatory capacity of immature DCs can be therefore utilized for the development of new immunotherapeutic strategies against atherosclerosis.

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

Cited by 48 publications

References 32 publications

Advances on Non-CD4 + Foxp3+ T Regulatory Cells

Advances on Non-CD4 + Foxp3+ T Regulatory Cells

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

Dendritic cells in atherosclerotic inflammation: the complexity of functions and the peculiarities of pathophysiological effects

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