A fail-safe mechanism for maintaining self-tolerance

doi:10.1084/jem.176.2.553

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A fail-safe mechanism for maintaining self-tolerance

S Guerder and P Matzinger
Basel Institute for Immunology, Switzerland.

Using cytotoxic T lymphocyte (CTL) responses to the class I histocompatibility antigen Qa1 and to the minor histocompatibility antigen H-Y, we show that the immune system maintains a peripheral screening process that is able to tolerize a wide variety of potentially autoimmune CTL. The critical factor is the presence or absence of specific T helper cells. If T help is available, CTL precursors that recognize antigen are activated. In the absence of help, they are tolerized. Thus, T helper cells are guardians of peripheral tolerance in CTL.
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Nowak, A. K., Robinson, B. W. S., Lake, R. A. (2003). Synergy between Chemotherapy and Immunotherapy in the Treatment of Established Murine Solid Tumors. Cancer Res. 63: 4490-4496 [Abstract] [Full Text]
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Wirths, S., Reichert, J., Grunebach, F., Brossart, P. (2002). Activated CD8+ T Lymphocytes Induce Differentiation of Monocytes to Dendritic Cells and Restore the Stimulatory Capacity of Interleukin 10-treated Antigen-presenting Cells. Cancer Res. 62: 5065-5068 [Abstract] [Full Text]
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Ronchese, F., Hermans, I. F. (2001). Killing of Dendritic Cells: A Life Cut Short or a Purposeful Death?. JEM 194: F23-F26 [Full Text]
Th. den Boer, A., Diehl, L., van Mierlo, G. J. D., van der Voort, E. I. H., Fransen, M. F., Krimpenfort, P., Melief, C. J. M., Offringa, R., Toes, R. E. M. (2001). Longevity of Antigen Presentation and Activation Status of APC Are Decisive Factors in the Balance Between CTL Immunity Versus Tolerance. J. Immunol. 167: 2522-2528 [Abstract] [Full Text]
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McNeel, D. G., Nguyen, L. D., Disis, M. L. (2001). Identification of T Helper Epitopes from Prostatic Acid Phosphatase. Cancer Res. 61: 5161-5167 [Abstract] [Full Text]
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Fischbein, M. P., Ardehali, A., Yun, J., Schoenberger, S., Laks, H., Irie, Y., Dempsey, P., Cheng, G., Fishbein, M. C., Bonavida, B. (2000). CD40 Signaling Replaces CD4+ Lymphocytes and Its Blocking Prevents Chronic Rejection of Heart Transplants. J. Immunol. 165: 7316-7322 [Abstract] [Full Text]
Hoffacker, V., Schultz, A., Tiesinga, J. J., Gold, R., Schalke, B., Nix, W., Kiefer, R., Muller-Hermelink, H. K., Marx, A. (2000). Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96: 3872-3879 [Abstract] [Full Text]
Cochlovius, B., Stassar, M., Christ, O., Raddrizzani, L., Hammer, J., Mytilineos, I., Zoller, M. (2000). In Vitro and In Vivo Induction of a Th Cell Response Toward Peptides of the Melanoma-Associated Glycoprotein 100 Protein Selected by the TEPITOPE Program. J. Immunol. 165: 4731-4741 [Abstract] [Full Text]
Schuurhuis, D. H., Laban, S., Toes, R. E.M., Ricciardi-Castagnoli, P., Kleijmeer, M. J., van der Voort, E. I.H., Rea, D., Offringa, R., Geuze, H. J., Melief, C. J.M., Ossendorp, F. (2000). Immature Dendritic Cells Acquire CD8+ Cytotoxic T Lymphocyte Priming Capacity upon Activation by T Helper Cell-independent or -dependent Stimuli. JEM 192: 145-150 [Abstract] [Full Text]
Lu, Z., Yuan, L., Zhou, X., Sotomayor, E., Levitsky, H. I., Pardoll, D. M. (2000). CD40-independent Pathways of T Cell Help for Priming of CD8+ Cytotoxic T Lymphocytes. JEM 191: 541-550 [Abstract] [Full Text]
Huang, Q., Richmond, J. F.L., Suzue, K., Eisen, H. N., Young, R. A. (2000). In Vivo Cytotoxic T Lymphocyte Elicitation by Mycobacterial Heat Shock Protein 70 Fusion Proteins Maps to a Discrete Domain and Is CD4+ T Cell Independent. JEM 191: 403-408 [Abstract] [Full Text]
Whitmire, J. K., Flavell, R. A., Grewal, I. S., Larsen, C. P., Pearson, T. C., Ahmed, R. (1999). CD40-CD40 Ligand Costimulation Is Required for Generating Antiviral CD4 T Cell Responses But Is Dispensable for CD8 T Cell Responses. J. Immunol. 163: 3194-3201 [Abstract] [Full Text]
Hermans, I. F., Ritchie, D. S., Daish, A., Yang, J., Kehry, M. R., Ronchese, F. (1999). Impaired Ability of MHC Class II-/- Dendritic Cells to Provide Tumor Protection is Rescued by CD40 Ligation. J. Immunol. 163: 77-81 [Abstract] [Full Text]
Ruedl, C., Kopf, M., Bachmann, M. F. (1999). CD8+ T Cells Mediate CD40-independent Maturation of Dendritic Cells In Vivo. JEM 189: 1875-1884 [Abstract] [Full Text]
Tillman, B. W., Gruijl, T. D. d., Bakker, S. A. L.-d., Scheper, R. J., Pinedo, H. M., Curiel, T. J., Gerritsen, W. R., Curiel, D. T. (1999). Maturation of Dendritic Cells Accompanies High-Efficiency Gene Transfer by a CD40-Targeted Adenoviral Vector. J. Immunol. 162: 6378-6383 [Abstract] [Full Text]
Overwijk, W. W., Lee, D. S., Surman, D. R., Irvine, K. R., Touloukian, C. E., Chan, C.-C., Carroll, M. W., Moss, B., Rosenberg, S. A., Restifo, N. P. (1999). Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: Requirement for CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 96: 2982-2987 [Abstract] [Full Text]
Bretscher, P. A. (1999). A two-step, two-signal model for the primary activation of precursor helper T cells. Proc. Natl. Acad. Sci. USA 96: 185-190 [Abstract] [Full Text]
ROSSINI, A. A., GREINER, D. L., MORDES, J. P. (1999). Induction of Immunologic Tolerance for Transplantation. Physiol. Rev. 79: 99-141 [Abstract] [Full Text]
De Veerman, M., Heirman, C., Van Meirvenne, S., Devos, S., Corthals, J., Moser, M., Thielemans, K. (1999). Retrovirally Transduced Bone Marrow-Derived Dendritic Cells Require CD4+ T Cell Help to Elicit Protective and Therapeutic Antitumor Immunity. J. Immunol. 162: 144-151 [Abstract] [Full Text]
Bennett, S. R.M., Carbone, F. R., Toy, T., Miller, J. F.A.P., Heath, W. R. (1998). B Cells Directly Tolerize CD8+ T Cells. JEM 188: 1977-1983 [Abstract] [Full Text]
Sigal, L. J., Reiser, H., Rock, K. L. (1998). The Role of B7-1 and B7-2 Costimulation for the Generation of CTL Responses In Vivo. J. Immunol. 161: 2740-2745 [Abstract] [Full Text]
Borrow, P., Tough, D. F., Eto, D., Tishon, A., Grewal, I. S., Sprent, J., Flavell, R. A., Oldstone, M. B.�A. (1998). CD40 Ligand-Mediated Interactions Are Involved in the Generation of Memory CD8+ Cytotoxic T Lymphocytes (CTL) but Are Not Required for the Maintenance of CTL Memory following Virus Infection. J. Virol. 72: 7440-7449 [Abstract] [Full Text]
Zelenika, D., Adams, E., Mellor, A., Simpson, E., Chandler, P., Stockinger, B., Waldmann, H., Cobbold, S. P. (1998). Rejection of H-Y Disparate Skin Grafts by Monospecific CD4+ Th1 and Th2 Cells: No Requirement for CD8+ T Cells or B Cells. J. Immunol. 161: 1868-1874 [Abstract] [Full Text]
Kurts, C., Miller, J. F.A.P., Subramaniam, R. M., Carbone, F. R., Heath, W. R. (1998). Major Histocompatibility Complex Class I-restricted Cross-presentation Is Biased towards High Dose Antigens and Those Released during Cellular Destruction. JEM 188: 409-414 [Abstract] [Full Text]
Bour, H., Horvath, C., Lurquin, C., Cerottini, J.-C., MacDonald, H. R. (1998). Differential Requirement for CD4 Help in the Development of an Antigen-Specific CD8+ T Cell Response Depending on the Route of Immunization. J. Immunol. 160: 5522-5529 [Abstract] [Full Text]
Heath, W. R., Kurts, C., Miller, J. F.A.P., Carbone, F. R. (1998). Cross-tolerance: A Pathway for Inducing Tolerance to Peripheral Tissue Antigens. JEM 187: 1549-1553 [Full Text]
McCarthy, S. A., Mainwaring, M. S., Dougall, D. S., Lamouse-Smith, E. S. (1998). Activation Requirements, Lytic Mechanism, and Development of a Novel Anti-CD8-Resistant CTL Population. J. Immunol. 160: 2715-2724 [Abstract] [Full Text]
Ehl, S., Hombach, J., Aichele, P., Rulicke, T., Odermatt, B., Hengartner, H., Zinkernagel, R., Pircher, H. (1998). Viral and Bacterial Infections Interfere with Peripheral Tolerance Induction and Activate CD8+ T Cells to Cause Immunopathology. JEM 187: 763-774 [Abstract] [Full Text]
Kurts, C., Carbone, F. R., Barnden, M., Blanas, E., Allison, J., Heath, W. R., Miller, J. F.A.P. (1997). CD4+ T Cell Help Impairs CD8+ T Cell Deletion Induced by Cross-presentation of Self-Antigens and Favors Autoimmunity. JEM 186: 2057-2062 [Abstract] [Full Text]
Kurts, C., Kosaka, H., Carbone, F. R., Miller, J. F.A.P., Heath, W. R. (1997). Class I-restricted Cross-Presentation of Exogenous Self-Antigens Leads to Deletion of Autoreactive CD8+ T Cells. JEM 186: 239-245 [Abstract] [Full Text]
Bennett, S. R.M., Carbone, F. R., Karamalis, F., Miller, J. F.A.P., Heath, W. R. (1997). Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help. JEM 186: 65-70 [Abstract] [Full Text]
Fuchs, E., Matzinger, P (1992). B cells turn off virgin but not memory T cells. Science 258: 1156-1159 [Abstract]