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Review
. 2010 Jul;47(1-3):143-52.
doi: 10.1007/s12026-009-8145-2.

Reconstitution of self-tolerance after hematopoietic stem cell transplantation

Allan D Hess  1
Affiliations
Review

Reconstitution of self-tolerance after hematopoietic stem cell transplantation

Allan D Hess. Immunol Res. 2010 Jul.

Abstract

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow or hematopoietic stem cell transplantation. GVHD is thought to be primarily due to the response of mature T cells transferred along with the bone marrow graft to foreign histocompatibility antigens expressed on host tissues. Recent studies, however, have challenged this paradigm set forth in the 1960s and have suggested that self-MHC class II antigens can be recognized in GVHD. Many questions still remain unanswered particularly in regard to the role of immune reconstitution, the ability to recognize and discriminate self and the re-establishment of self-tolerance. In fact, the failure to re-establish tolerance to self can lead to systemic autoimmunity that may exacerbate or even mimic GVHD. The present review summarizes our studies in autologous GVHD characterizing the underlying immune mechanisms and their potential impact in allogeneic hematopoietic stem cell transplantation.

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Figures

Fig. 1
Fig. 1
Potential interactions between allogeneic and autologous GVHD. Alloreactive T cells recognize and respond to histocompatibility antigen differences in the host and can damage the thymic epithelium. In addition, administration of CsA alters T cell differentiation in the thymus. Both processes inhibit thymic-dependent clonal deletion inducing the release of autoreactive T cells that can potentiate allogeneic GVHD and induce an autoaggression that is virtually identical to allogeneic GVHD
Fig. 2
Fig. 2
Recognition of the MHC class II–CLIP complex in autologous GVHD. Autologous GVHD effector T cells recognize MHC class II antigens presenting a peptide from the invariant chain, termed CLIP. In addition to recognition of the MHC class II binding domain of CLIP, the N-terminal flanking domain appears to interact with the Vβ chain of the T cell receptor at or near the binding site for the SEB super antigen
Fig. 3
Fig. 3
Development of donor to host and self-tolerance. Reconstitution of the regulatory compartment allows for the down regulation of alloreactive and autoreactive T cells. CD4+ CD25+ Foxp3+ T cells activated by APCs may orchestrate the establishment of immune tolerance. CD8+ CD28– regulatory T cells may also interact to facilitate this state of unresponsiveness
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References

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