Immune tolerance to self-major histocompatibility complex class II antigens after bone marrow transplantation: role of regulatory T cells

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Allan D Hess, Christopher J Thoburn

Abstract

The immune system undergoes rapid reconstitution after autologous or syngeneic bone marrow transplantation with the re-establishment of tolerance to self-antigens. Administration of drugs such as cyclosporine that inhibit thymic-dependent clonal deletion disrupts the reconstitution of the immune system. In the absence of a peripheral regulatory T cells eliminated by the preparative regimen, systemic autoimmunity with pathology similar to graft-versus-host disease often develops. Moreover, the resolution of autoaggression is dependent on the reconstitution of CD4+ regulatory T cells. This study examined the specificity and function of this regulatory population assessed ex vivo that plays a critical role in down-regulating the autoreactive T lymphocyte response in cyclosporine-induced syngeneic graft-versus-host disease. The results suggest that both the antigen-specific regulatory and pathogenic effector T cells recognize a common peptide antigen framework (CLIP, a peptide derived from the invariant chain) presented by major histocompatibility complex class II molecules. Analysis of the CD4+ T-cell compartment revealed two subsets of CLIP-reactive T cells that differentially require the N- and C-terminal flanking domain of this...Continue Reading

References

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Citations

Sep 3, 2008·Bone Marrow Transplantation·W R DrobyskiW Grossman
Dec 1, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sebastian GüntherChristian Freund
Oct 21, 2006·Current Opinion in Hematology·Kristin Baird, Steven Z Pavletic
Nov 18, 2011·Clinical and Vaccine Immunology : CVI·Donald C VinhCiriaco A Piccirillo
Jul 17, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·J Anthony BrandonJ Scott Bryson
Jan 10, 2006·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Allan D Hess
Sep 23, 2008·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Kristin M PageJoanne Kurtzberg
Mar 12, 2008·Bone Marrow Transplantation·S J OhS Park
Feb 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Anthony BrandonJ Scott Bryson

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