Induction of FoxP3+CD4+CD25+ regulatory T cells by a bone marrow population distinct from plasmacytoid-DC

Taylor, K. B.; Laszkowska, Monika; Cohick, Evan; Colson, Yolonda L.

doi:10.1016/j.cellimm.2008.03.003

Cited by 10 publications

(9 citation statements)

References 34 publications

(84 reference statements)

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“…To test the first possibility, we examined whether facilitating cells (Gandy et al, 1999; Kaufman et al, 1994), regulatory T cells (Taylor et al, 2008), or other cells produced during culture supported allograft. It has been established that unique differentiated BM populations as facilitating cells improve allogeneic reconstitution and result in donor-specific transplantation tolerance across MHC disparities (Gandy et al, 1999; Kaufman et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

“…The reported facilitating cells express conventional T cell components such as CD8 but are not T cells as they do not express TCR (Kaufman et al, 1994),(Bridenbaugh et al, 2008). Interestingly, facilitating cells induce an increase in numbers of donor regulatory T cells (Treg) (Taylor et al, 2008), which directly facilitate allograft. While freshly isolated HSCs do not contain CD3 + cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

et al. 2011

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Summary The lack of understanding of the interplay between hematopoietic stem cells (HSCs) and the immune system has severely hampered the stem cell research and practice of transplantation. Major problems for allogeneic transplantation include low levels of donor engraftment and high risks of graft-versus-host disease (GVHD). Transplantation of purified allogeneic HSCs diminishes the risk of GVHD, but results in decreased engraftment. Here we show that ex vivo expanded mouse HSCs efficiently overcame the major histocompatibility complex barrier and repopulated allogeneic recipient mice. An 8-day expansion culture led to a 40-fold increase of the allograft ability of HSCs. Both increased numbers of HSCs and culture-induced elevation of expression of the immune inhibitor CD274 (B7-H1 or PD-L1) on the surface of HSCs contributed to the enhancement. Our study indicates the great potential of utilizing ex vivo expanded HSCs for allogeneic transplantation, and suggests that the immune privilege of HSCs can be modulated.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

et al. 2011

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“…Recent evidence has accumulated that DCs stimulate the expansion of T reg that suppress the autoimmune response (Li et al 2008; Swee et al 2009; Taylor et al 2008; Yamazaki et al 2009). It is well recognized that self-tolerance involves suppression by CD4 + CD25 + FoxP3 + Treg cells.…”

Section: Discussionmentioning

confidence: 99%

“…Third, administration of the cytokine fms-like tyrosine kinase 3 ligand (Flt3L) increased the population of CD8α + DCs and reduced incidence of autoimmune diabetes in mice (O’Keeffe et al 2005; O’Keeffe et al 2002). Lastly, DCs directly induce T reg and thus could contribute to the suppression of autoimmunity (Li et al 2008; Swee et al 2009; Taylor et al 2008; Yamazaki et al 2009). We surmised that if DCs play a central role in autoimmunity, specifically increasing the quantity of CD8α + DCs could result in tolerance and protection against the arthritis.…”

Section: Introductionmentioning

confidence: 99%

CD8α+ dendritic cells improve collagen-induced arthritis in CC chemokine receptor (CCR)-2 deficient mice

et al. 2011

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Objective Dendritic cells (DCs) have long been recognized as potential therapeutic targets of rheumatoid arthritis (RA). Increasing evidence has showed that DCs are capable of suppressing autoimmunity by expanding FoxP3+ regulatory T cells (Treg), which in turn exert immunosuppression by increasing TGFβ-1. In the SKG mice, activated DC prime autoreactive T cells causing autoantibody production and an inflammatory arthritic response. Recently, we reported that CC-chemokine receptor-2 deficient (Ccr2−/−) mice had impaired DCs migration and reduced CD8α+ DCs in the C57Bl/6J mice strain and that these mice were more susceptible to collagen antibody-induced arthritis (CAIA), compared to wild type mice. To examine the mechanism by which DCs contribute to the increased susceptibility of arthritis in Ccr2−/− mice, we tested the hypothesis that CD8α+ DCs are protective (tolerogenic) against autoimmune arthritis by examining the role of CD8α+ DCs in Ccr2−/− and SKG mice. Methods To examine the mechanism by which DCs defects lead to the development of arthritis, we used two murine models of experimental arthritis: collagen-induced arthritis (CIA) in DBA1/J mice and zymosan-induced arthritis in SKG mice. DBA1/J mice received recombinant Flt3L-injections to expand endogenous DCs populations or adoptive transfers of CD8α+ DCs. Results Flt3L-mediated expansion of endogenous CD8α+ DCs resulted in heightened susceptibility of CIA. In contrast, supplementation with exogenous CD8α+ DCs ameliorated arthritis in Ccr2−/− mice and enhanced TGFβ1 production by T cells. Furthermore, SKG mice with genetic inactivation of CCR2 did not affect the numbers of DCs nor improve the arthritis phenotype. Conclusion CD8α+ DCs were tolerogenic to the development of arthritis. CD8α+ DCs deficiency heightened the sensitivity to arthritis in Ccr2−/− mice. Ccr2 deficiency did not alter the arthritic phenotype in SKG mice suggesting the arthritis in Ccr2−/− mice was T cell-independent.

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“…/CD25 ? T-regs cells in vitro [51] and potent antigen-specific immune regulation in vivo [52]. Thus FCs may be a future attractive source to address the primary challenge in translating cell-based therapies to the clinic: maintaining tolerogenic features after transplantation while avoiding GvHD [26 • ].…”

Section: Discussionmentioning

confidence: 99%

Minimization of Immunosuppression and Tolerance Induction in Reconstructive Transplantation

et al. 2012

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Vascularized composite allotransplantation (VCA) is an innovative reconstructive modality for patients sustaining complex injuries not amenable to conventional treatment. Advances in immunosuppression have made VCA a clinical reality and a valid reconstructive option for such patients. The requirement, however, for multi-drug high-dose immunosuppressive regimens with their numerous side effects has hindered widespread clinical application of VCA. There is thus a need for novel immunologic modalities to minimize or even obviate the need for immunosuppression (tolerance induction) while still preserving the allograft and preventing rejection. Recent advances in targeted immunotherapy and cell-based protocols were able to achieve tolerance in selected cases of solid organ transplantation. This paved the way for innovative immunomodulatory protocols now also applied to VCA that aim for minimal immunosuppression or for induction of donor-specific tolerance. These concepts and novel protocols will be discussed in this review.

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Induction of FoxP3+CD4+CD25+ regulatory T cells by a bone marrow population distinct from plasmacytoid-DC

Cited by 10 publications

References 34 publications

Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

Ex Vivo Expanded Hematopoietic Stem Cells Overcome the MHC Barrier in Allogeneic Transplantation

CD8α+ dendritic cells improve collagen-induced arthritis in CC chemokine receptor (CCR)-2 deficient mice

Minimization of Immunosuppression and Tolerance Induction in Reconstructive Transplantation

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