Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 November 1989:
Vol. 246. no. 4933, pp. 1038 - 1041
DOI: 10.1126/science.2511629
Prev | Table of Contents | Next

Articles

Science, Vol 246, Issue 4933, 1038-1041
Copyright © 1989 by American Association for the Advancement of Science

articles

A nondeletional mechanism of thymic self tolerance

F Ramsdell, T Lantz, and BJ Fowlkes

Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892.

T cells become tolerant of self antigens during their development in the thymus. Clonal deletion of thymocytes bearing self-reactive T cell receptors is a major mechanism for generating tolerance and occurs readily for antigens expressed by bone marrow-derived cells. Tolerance to antigens expressed on the radioresistant thymic stromal elements is demonstrated here to occur via a nondeletional mechanism. For minor lymphocyte stimulatory (Mls-1a) and major histocompatibility complex (MHC) antigens, this alternate form of tolerance induction results in clonal anergy.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Immunobiology of Heart and Heart-Lung Transplantation.
B. P. Griffith, M. Haddad, and R. S. Poston (2008)
Card. Surg. Adult 3, 1513-1538
   Full Text »
Shaping of the Autoreactive Regulatory T Cell Repertoire by Thymic Cortical Positive Selection.
J. Ribot, G. Enault, S. Pilipenko, A. Huchenq, M. Calise, D. Hudrisier, P. Romagnoli, and J. P. M. van Meerwijk (2007)
J. Immunol. 179, 6741-6748
   Abstract »    Full Text »    PDF »
Modulation of CD4 co-receptor limits spontaneous autoimmunity when high-affinity transgenic TCR specific for self-antigen is expressed on a genetically resistant background.
Z. Illes, H. Waldner, J. Reddy, A. C. Anderson, R. A. Sobel, and V. K. Kuchroo (2007)
Int. Immunol. 19, 1235-1248
   Abstract »    Full Text »    PDF »
Agonist Ligands Expressed by Thymic Epithelium Enhance Positive Selection of Regulatory T Lymphocytes from Precursors with a Normally Diverse TCR Repertoire.
J. Ribot, P. Romagnoli, and J. P. M. van Meerwijk (2006)
J. Immunol. 177, 1101-1107
   Abstract »    Full Text »    PDF »
Molecular Signature of Recent Thymic Selection Events on Effector and Regulatory CD4+ T Lymphocytes.
P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk (2005)
J. Immunol. 175, 5751-5758
   Abstract »    Full Text »    PDF »
Plasticity in the positive selection of T cells: affinity of the selecting antigen and IL-7 affect T cell responsiveness.
R. L. Rubin and T. M. Hermanson (2005)
Int. Immunol. 17, 959-971
   Abstract »    Full Text »    PDF »
CTLA-4 Engagement Acts as a Brake on CD4+ T Cell Proliferation and Cytokine Production but Is Not Required for Tuning T Cell Reactivity in Adaptive Tolerance.
M. Inobe and R. H. Schwartz (2004)
J. Immunol. 173, 7239-7248
   Abstract »    Full Text »    PDF »
Self-Specific MHC Class II-Restricted CD4-CD8- T Cells That Escape Deletion and Lack Regulatory Activity.
C. Viret and C. A. Janeway Jr. (2003)
J. Immunol. 170, 201-209
   Abstract »    Full Text »    PDF »
Immunobiology of Heart and Heart-Lung Transplantation.
B. P. Griffith and R. S. Poston (2003)
Card. Surg. Adult 2, 1403-1426
   Full Text »
Preferential Recognition of Self Antigens Despite Normal Thymic Deletion of CD4+CD25+ Regulatory T Cells.
P. Romagnoli, D. Hudrisier, and J. P. M. van Meerwijk (2002)
J. Immunol. 168, 1644-1648
   Abstract »    Full Text »    PDF »
Induction of tolerance in autoimmune diseases by hematopoietic stem cell transplantation: getting closer to a cure?.
R. K. Burt, S. Slavin, W. H. Burns, and A. M. Marmont (2002)
Blood 99, 768-784
   Abstract »    Full Text »    PDF »
Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide.
L. Luznik, S. Jalla, L. W. Engstrom, R. Iannone, and E. J. Fuchs (2001)
Blood 98, 3456-3464
   Abstract »    Full Text »    PDF »
Major Histocompatibility Complex Class II-positive Cortical Epithelium Mediates the Selection of CD4+25+ Immunoregulatory T Cells.
S. J. Bensinger, A. Bandeira, M. S. Jordan, A. J. Caton, and T. M. Laufer (2001)
J. Exp. Med. 194, 427-438
   Abstract »    Full Text »    PDF »
Modulation of CD8+ T Cell Response to Antigen by the Levels of Self MHC Class I.
F. R. Santori, I. Arsov, and S. Vukmanovic (2001)
J. Immunol. 166, 5416-5421
   Abstract »    Full Text »    PDF »
A Role for Accessibility to Self-Peptide-Self-MHC Complexes in Intrathymic Negative Selection.
C. Viret, D. B. Sant'Angelo, X. He, H. Ramaswamy, and C. A. Janeway Jr. (2001)
J. Immunol. 166, 4429-4437
   Abstract »    Full Text »    PDF »
A Physiological Ligand of Positive Selection Is Recognized as a Weak Agonist.
R. E. Berg, S. Irion, S. Kattman, M. F. Princiotta, and U. D. Staerz (2000)
J. Immunol. 165, 4209-4216
   Abstract »    Full Text »    PDF »
A Self MHC Class II {beta}-Chain Peptide Prevents Diabetes in Nonobese Diabetic Mice.
P. Chaturvedi, B. Agrawal, M. Zechel, E. Lee-Chan, and B. Singh (2000)
J. Immunol. 164, 6610-6620
   Abstract »    Full Text »    PDF »
A Physiological Ligand of Positive Selection Is Seen with High Specificity.
S. Irion, R. E. Berg, and U. D. Staerz (2000)
J. Immunol. 164, 4601-4606
   Abstract »    Full Text »    PDF »
Functional comparison of thymic B cells and dendritic cells in vivo.
P. Kleindienst, I. Chretien, T. Winkler, and T. Brocker (2000)
Blood 95, 2610-2616
   Abstract »    Full Text »    PDF »
A Population of In Vivo Anergized T Cells with a Lower Activation Threshold for the Induction of CD25 Exhibit Differential Requirements in Mobilization of Intracellular Calcium and Mitogen-Activated Protein Kinase Activation.
O. Utting, S.-J. Teh, and H.-S. Teh (2000)
J. Immunol. 164, 2881-2889
   Abstract »    Full Text »    PDF »
In Vivo CD4+ T Cell Tolerance Induction Versus Priming Is Independent of the Rate and Number of Cell Divisions.
A. J. Adler, C.-T. Huang, G. S. Yochum, D. W. Marsh, and D. M. Pardoll (2000)
J. Immunol. 164, 649-655
   Abstract »    Full Text »    PDF »
In Vivo T-Lymphocyte Tolerance in the Absence of Thymic Clonal Deletion Mediated by Hematopoietic Cells.
J. P.M. van Meerwijk and H. R. MacDonald (1999)
Blood 93, 3856-3862
   Abstract »    Full Text »    PDF »
Induction of Immunologic Tolerance for Transplantation.
A. A. ROSSINI, D. L. GREINER, and J. P. MORDES (1999)
Physiol Rev 79, 99-141
   Abstract »    Full Text »    PDF »
CD4+ T Cell Tolerance to Parenchymal Self-Antigens Requires Presentation by Bone Marrow-derived Antigen-presenting Cells.
A. J. Adler, D. W. Marsh, G. S. Yochum, J. L. Guzzo, A. Nigam, W. G. Nelson, and D. M. Pardoll (1998)
J. Exp. Med. 187, 1555-1564
   Abstract »    Full Text »    PDF »
Identification of T-Cell Epitopes on the Rhesus Polypeptides in Autoimmune Hemolytic Anemia.
R. N. Barker, A. M. Hall, G. R. Standen, J. Jones, and C. J. Elson (1997)
Blood 90, 2701-2715
   Abstract »    Full Text »    PDF »
Transferable Anergy: Superantigen Treatment Induces CD4+ T Cell Tolerance That Is Reversible and Requires CD4-CD8- Cells and Interferon gamma.
L. S. Cauley, K. A. Cauley, F. Shub, G. Huston, and S. L. Swain (1997)
J. Exp. Med. 186, 71-81
   Abstract »    Full Text »    PDF »
Maintenance of in Vivo Tolerance by Persistence of Antigen.
F. Ramsdell and B. J. Fowlkes (1992)
Science 257, 1130-1134
   Abstract »    PDF »
Transactivation by AP-1 Is a Molecular Target of T Cell Clonal Anergy.
S.-M. Kang, B. Beverly, A.-C. Tran, K. Brorson, R. H. Schwartz, and M. J. Lenardot (1992)
Science 257, 1134-1138
   Abstract »    PDF »
Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth.
A. Posselt, C. Barker, A. Friedman, and A Naji (1992)
Science 256, 1321-1324
   Abstract »    PDF »
Evidence for the effects of a superantigen in rheumatoid arthritis.
X Paliard, S. West, J. Lafferty, Clements JR, J. Kappler, P Marrack, and B. Kotzin (1991)
Science 253, 325-329
   Abstract »    PDF »
Induction of self-tolerance in T cells but not B cells of transgenic mice expressing little self antigen.
S Adelstein, H Pritchard-Briscoe, T. Anderson, J Crosbie, G Gammon, R. Loblay, A Basten, and C. Goodnow (1991)
Science 251, 1223-1225
   Abstract »    PDF »
Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production.
G. Otten and R. Germain (1991)
Science 251, 1228-1231
   Abstract »    PDF »
Peripheral clonal elimination of functional T cells.
L. Jones, L. Chin, D. Longo, and A. Kruisbeek (1990)
Science 250, 1726-1729
   Abstract »    PDF »
Induction of neonatal tolerance to Mlsa antigens by CD8+ T cells.
Webb SR and J Sprent (1990)
Science 248, 1643-1646
   Abstract »    PDF »
The role of the T cell receptor in positive and negative selection of developing T cells.
M Blackman, J Kappler, and P Marrack (1990)
Science 248, 1335-1341
   Abstract »    PDF »
Clonal deletion versus clonal anergy: the role of the thymus in inducing self tolerance.
F Ramsdell and B. Fowlkes (1990)
Science 248, 1342-1348
   Abstract »    PDF »
A cell culture model for T lymphocyte clonal anergy.
R. Schwartz (1990)
Science 248, 1349-1356
   Abstract »    PDF »
T cell reactivity to MHC molecules: immunity versus tolerance.
J Sprent, E. Gao, and S. Webb (1990)
Science 248, 1357-1363
   Abstract »    PDF »
Tolerance in transgenic mice expressing major histocompatibility molecules extrathymically on pancreatic cells.
L. Burkly, D Lo, and R. Flavell (1990)
Science 248, 1364-1368
   Abstract »    PDF »
Self-nonself discrimination by T cells.
H von Boehmer and P Kisielow (1990)
Science 248, 1369-1373
   Abstract »    PDF »
Mechanisms of immunological tolerance.
H. MacDonald (1989)
Science 246, 982
   PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)