Tolerance and suppression in a primed immune system

Transplantation
S E MarshallH Waldmann

Abstract

The induction of tolerance in a primed immune system would be valuable therapeutically, but has been difficult to achieve. Mice primed to multiple minor histoincompatible antigens (minors) are able to rapidly reject secondary grafts using either their CD4+ or CD8+ T-cell subpopulations. Short courses of treatment with nonlytic anti-CD4 and anti-CD8 antibodies targeted at both T-cell subsets can induce long-term peripheral T-cell tolerance in primed mice. We examine the mechanisms by which peripheral tolerance is maintained, and show that tolerant mice harbor CD4+ T cells capable of specifically suppressing rejection mediated by either subset of primed T cells. Remarkably, elimination of CD4+ T cells from tolerant mice resulted in graft rejection, suggesting that graft-reactive CD8+ T cells had not been eliminated, but had been under continuous regulation by "tolerant" CD4+ T cells. This result demonstrates that it may be possible to establish therapeutic operational tolerance without permanently inactivating all antigen-reactive cells.

References

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Citations

Sep 9, 2008·Journal of Clinical Immunology·Herman WaldmannStephen Cobbold
Jul 6, 2000·Human Immunology·L S Taams, M H Wauben
Sep 23, 2003·Current Opinion in Immunology·Luis GracaHerman Waldmann
Oct 31, 1998·Current Opinion in Immunology·S Cobbold, H Waldmann
Oct 6, 1999·Current Opinion in Immunology·Y Zhai, J W Kupiec-Weglinski
Dec 24, 2003·Seminars in Immunology·Stephen P CobboldHerman Waldmann
Aug 31, 2011·The Journal of Experimental Medicine·Adrian R KendalHerman Waldmann
May 23, 1998·Annual Review of Immunology·H Waldmann, S Cobbold
Apr 3, 2014·The Journal of Clinical Investigation·Herman WaldmannStephen Cobbold
Aug 23, 2002·Immunological Reviews·Herman Waldmann
Jul 1, 1997·European Journal of Immunology·R ScullyH Waldmann
Nov 18, 2003·Immunological Reviews·Stephen P CobboldHerman Waldmann
Aug 15, 2006·Immunological Reviews·Herman WaldmannStephen Cobbold
Sep 16, 2006·Immunological Reviews·Stephen P CobboldHerman Waldmann
Mar 5, 2005·Trends in Immunology·Luis GracaHerman Waldmann
Feb 16, 2006·Seminars in Immunology·Herman WaldmannPaul J Fairchild
May 17, 2005·Microbes and Infection·Ehud Hauben, Maria Grazia Roncarolo
Oct 22, 2002·Expert Opinion on Therapeutic Targets·Stephen P Cobbold
Jul 26, 2005·Cytotherapy·E HaubenM G Roncarolo
Nov 5, 2002·Nature Immunology·Chun-Yen LinHerman Waldmann
Oct 15, 1998·Transplantation·S SeiterM Zöller
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S ArtikE Gleichmann
Oct 8, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Osquel Barroso HerreraRobert I Lechler
Jan 29, 1999·Physiological Reviews·A A RossiniJ P Mordes
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J M PhillipsA Cooke
Jun 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masaaki KataokaM Wayne Flye
May 23, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B KeJ W Kupiec-Weglinski
Nov 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A YamadaH Auchincloss

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