Long-Term Control of Alloreactive B Cell Responses by the Suppression of T Cell Help

Li, Yijin; Ma, Lianli; Yin, Dengping; Shen, Jikun; Chong, Anita S.

doi:10.4049/jimmunol.180.9.6077

Cited by 18 publications

(15 citation statements)

References 51 publications

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“…Other recipients, who were not known to be sensitized, develop antibodies against donor HLA antigens some time after transplantation [12]. The detection of antibodies against HLA in the serum after transplantation may depend on a balance between production of antibodies by plasma cells, sequestration of antibody by the transplanted organ and possibly the effect of regulatory factors that inhibit antibody production [13]. We would like to know whether in vitro production of anti-donor HLA antibodies by B cells might be detectable before such antibodies appear in the serum.…”

Section: Discussionmentioning

confidence: 98%

Peripheral blood B cells producing donor-specific HLA antibodies in vitro

et al. 2009

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Section: Discussionmentioning

confidence: 98%

Peripheral blood B cells producing donor-specific HLA antibodies in vitro

et al. 2009

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“…Intracellular expression of an antigen was sufficient to induce T cell tolerance in mice (Tian et al 2003). Expressing dominant T cell epitopes of allergens on the surface of HSC would conceivably avoid the risk of anaphylaxis, provided that T cell tolerance is sufficient to induce B cell tolerance, as it has been described (Li et al 2008). Use of small peptides would also facilitate fusion of several dominant T cell epitopes of various allergens to achieve protection toward several allergens at the same time.…”

Section: Avoiding Anaphylaxismentioning

confidence: 93%

Cell-Based Therapy in Allergy

Baranyi

Gattringer

Valenta

et al. 2011

Vaccines Against Allergies

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IgE-mediated allergy is an immunological disorder occurring in response to otherwise harmless environmental antigens (i.e., allergens). Development of effective therapeutic or preventive approaches inducing robust tolerance toward allergens remains an unmet goal. Several experimental tolerance approaches have been described. The therapeutic use of regulatory T cells (Tregs) and the establishment of molecular chimerism are two cell-based strategies that are of particular interest. Treg therapy is close to clinical application, but its efficacy remains to be fully defined. Recent proof-of-concept studies demonstrated that transplantation of syngeneic hematopoietic stem cells modified in vitro to express a major allergen leads to molecular chimerism and robust allergen-specific tolerance. Here we review cell-based tolerance strategies in allergy, discussing their potentials and limitations.

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“…Early studies addressing peripheral mechanisms of B-cell tolerance by Li et al . (193–196) have used the alloreactive 3–83 BCR-transgenic mice to track alloreactive B cells in vivo. Peripheral deletion of alloreactive B cells and suppression of T-cell help were reported to be the bases for B-cell hyporesponsiveness in the model cardiac allograft tolerance induced by anti-CD154/DST.…”

Section: Alloreactive B-cell Tolerance Mechanisms and Their Stabilitymentioning

confidence: 99%

Transplantation tolerance and its outcome during infections and inflammation

Chong

Alegre

2014

Immunological Reviews

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Summary Much progress has been made towards understanding the mechanistic basis of transplantation tolerance in experimental models, which includes clonal deletion of alloreactive T and B cells, induction of cell-intrinsic hyporesponsiveness, and dominant regulatory cells that mediate infectious tolerance and linked-suppression. Despite encouraging success in the laboratory, achieving tolerance in the clinic remains challenging, but the basis for these challenges are beginning to be understood. Heterologous memory alloreactive T cells generated by infections prior to transplantation have been shown to be a critical barrier to tolerance induction. Furthermore, infections at the time of transplantation and tolerance induction provide a pro-inflammatory milieu that alters the stability and function of regulatory T cells as well as the activation requirements and differentiation of effector T cells. Thus infections can result in enhanced alloreactivity, resistance to tolerance induction, and destabilization of the established tolerance state. We speculate that these experimental findings have relevance to the clinic, where infections have been associated with allograft rejection and may be a causal event precipitating the loss of grafts after long-periods of stable operational tolerance. Understanding the mechanisms by which infections prevent and destabilize tolerance can lead to therapies that promote stable lifelong tolerance in transplant recipients.

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Long-Term Control of Alloreactive B Cell Responses by the Suppression of T Cell Help

Cited by 18 publications

References 51 publications

Peripheral blood B cells producing donor-specific HLA antibodies in vitro

Peripheral blood B cells producing donor-specific HLA antibodies in vitro

Cell-Based Therapy in Allergy

Transplantation tolerance and its outcome during infections and inflammation

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