J. Exp. Med., Volume 188, Number 11, December 7, 1998 1977-1983

B Cells Directly Tolerize CD8⁺ T Cells

By Sally R.M. Bennett,^* Francis R. Carbone,^§ Tracey Toy,^§ Jacques F.A.P. Miller,^* and William R. Heath^*

From the ^* Immunology Division, The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia;  The Cooperative Research Centre for Vaccine Technology at the Queensland Institute of Medical Research, The Royal Brisbane Hospital, Herston, Queensland 4029, Australia; and the ^§ Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria 3181, Australia

This report investigates the response of CD8⁺ T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the K^b-restricted ovalbumin (OVA) determinant OVA_257-264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro-activated CD8⁺ T cells from the K^b-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8⁺ T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Tretter, T., Venigalla, R. K. C., Eckstein, V., Saffrich, R., Sertel, S., Ho, A. D., Lorenz, H.-M. (2008). Induction of CD4+ T-cell anergy and apoptosis by activated human B cells. Blood 112: 4555-4564 [Abstract] [Full Text]  
• Fehr, T., Wang, S., Haspot, F., Kurtz, J., Blaha, P., Hogan, T., Chittenden, M., Wekerle, T., Sykes, M. (2008). Rapid Deletional Peripheral CD8 T Cell Tolerance Induced by Allogeneic Bone Marrow: Role of Donor Class II MHC and B Cells. J. Immunol. 181: 4371-4380 [Abstract] [Full Text]  
• Fehr, T., Haspot, F., Mollov, J., Chittenden, M., Hogan, T., Sykes, M. (2008). Alloreactive CD8 T Cell Tolerance Requires Recipient B Cells, Dendritic Cells, and MHC Class II. J. Immunol. 181: 165-173 [Abstract] [Full Text]  
• Ashour, H. M., Seif, T. M. (2007). The role of B cells in the induction of peripheral T cell tolerance. J. Leukoc. Biol. 82: 1033-1039 [Full Text]  
• Bijker, M. S., van den Eeden, S. J. F., Franken, K. L., Melief, C. J. M., Offringa, R., van der Burg, S. H. (2007). CD8+ CTL Priming by Exact Peptide Epitopes in Incomplete Freund's Adjuvant Induces a Vanishing CTL Response, whereas Long Peptides Induce Sustained CTL Reactivity. J. Immunol. 179: 5033-5040 [Abstract] [Full Text]  
• Werner-Klein, M., Dresch, C., Marconi, P., Brocker, T. (2007). Transcriptional Targeting of B Cells for Induction of Peripheral CD8 T Cell Tolerance. J. Immunol. 178: 7738-7746 [Abstract] [Full Text]  
• Chung, Y., Kim, B.-S., Kim, Y.-J., Ko, H.-J., Ko, S.-Y., Kim, D.-H., Kang, C.-Y. (2006). CD1d-Restricted T Cells License B Cells to Generate Long-Lasting Cytotoxic Antitumor Immunity In vivo.. Cancer Res. 66: 6843-6850 [Abstract] [Full Text]  
• Su, H., Chang, D. S., Gambhir, S. S., Braun, J. (2006). Monitoring the Antitumor Response of Naive and Memory CD8 T Cells in RAG1-/- Mice by Positron-Emission Tomography. J. Immunol. 176: 4459-4467 [Abstract] [Full Text]  
• Bezbradica, J. S., Stanic, A. K., Matsuki, N., Bour-Jordan, H., Bluestone, J. A., Thomas, J. W., Unutmaz, D., Van Kaer, L., Joyce, S. (2005). Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo. J. Immunol. 174: 4696-4705 [Abstract] [Full Text]  
• Takacs, K., Du Roure, C., Nabarro, S., Dillon, N., McVey, J. H., Webster, Z., MacNeil, A., Bartok, I., Higgins, C., Gray, D., Merkenschlager, M., Fisher, A. G. (2004). The regulated long-term delivery of therapeutic proteins by using antigen-specific B lymphocytes. Proc. Natl. Acad. Sci. USA 101: 16298-16303 [Abstract] [Full Text]  
• Mellor, A. L., Chandler, P., Baban, B., Hansen, A. M., Marshall, B., Pihkala, J., Waldmann, H., Cobbold, S., Adams, E., Munn, D. H. (2004). Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int Immunol 16: 1391-1401 [Abstract] [Full Text]  
• von Bergwelt-Baildon, M., Schultze, J. L., Maecker, B., Menezes, I., Nadler, L. M., Lapointe, R., Thibodeau, J., Hwu, P. (2004). Correspondence re R. Lapointe et al., CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells. Cancer Res 2003;63:2836-43.. Cancer Res. 64: 4055-4057 [Full Text]  
• Coughlin, C. M., Vance, B. A., Grupp, S. A., Vonderheide, R. H. (2004). RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy. Blood 103: 2046-2054 [Abstract] [Full Text]  
• Parekh, V. V., Prasad, D. V. R., Banerjee, P. P., Joshi, B. N., Kumar, A., Mishra, G. C. (2003). B Cells Activated by Lipopolysaccharide, But Not By Anti-Ig and Anti-CD40 Antibody, Induce Anergy in CD8+ T Cells: Role of TGF-{beta}1. J. Immunol. 170: 5897-5911 [Abstract] [Full Text]  
• Lapointe, R., Bellemare-Pelletier, A., Housseau, F., Thibodeau, J., Hwu, P. (2003). CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells. Cancer Res. 63: 2836-2843 [Abstract] [Full Text]  
• Lazdina, U., Alheim, M., Nystrom, J., Hultgren, C., Borisova, G., Sominskaya, I., Pumpens, P., Peterson, D. L., Milich, D. R., Sallberg, M. (2003). Priming of cytotoxic T cell responses to exogenous hepatitis B virus core antigen is B cell dependent. J. Gen. Virol. 84: 139-146 [Abstract] [Full Text]  
• Riedl, P., El Kholy, S., Reimann, J., Schirmbeck, R. (2002). Priming Biologically Active Antibody Responses Against an Isolated, Conformational Viral Epitope by DNA Vaccination. J. Immunol. 169: 1251-1260 [Abstract] [Full Text]  
• Li, L., Liu, D., Hutt-Fletcher, L., Morgan, A., Masucci, M. G., Levitsky, V. (2002). Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage-colony-stimulating factor and interleukin-4. Blood 99: 3725-3734 [Abstract] [Full Text]  
• Paroli, M., Accapezzato, D., Francavilla, V., Insalaco, A., Plebani, A., Balsano, F., Barnaba, V. (2002). Long-lasting memory-resting and memory-effector CD4+ T cells in human X-linked agammaglobulinemia. Blood 99: 2131-2137 [Abstract] [Full Text]  
• Kawahata, K., Misaki, Y., Yamauchi, M., Tsunekawa, S., Setoguchi, K., Miyazaki, J.-i., Yamamoto, K. (2002). Peripheral Tolerance to a Nuclear Autoantigen: Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State of CD4+ Autoreactive T Cells After Proliferation. J. Immunol. 168: 1103-1112 [Abstract] [Full Text]  
• Lazdina, U., Cao, T., Steinbergs, J., Alheim, M., Pumpens, P., Peterson, D. L., Milich, D. R., Leroux-Roels, G., Sallberg, M. (2001). Molecular Basis for the Interaction of the Hepatitis B Virus Core Antigen with the Surface Immunoglobulin Receptor on Naive B Cells. J. Virol. 75: 6367-6374 [Abstract] [Full Text]  
• Keech, C. L., Farris, A. D., Beroukas, D., Gordon, T. P., McCluskey, J. (2001). Cognate T Cell Help Is Sufficient to Trigger Anti-Nuclear Autoantibodies in Naive Mice. J. Immunol. 166: 5826-5834 [Abstract] [Full Text]  
• Mizoguchi, E., Mizoguchi, A., Preffer, F. I., Bhan, A. K. (2000). Regulatory role of mature B cells in a murine model of inflammatory bowel disease. Int Immunol 12: 597-605 [Abstract] [Full Text]  
• Evans, D. E., Munks, M. W., Purkerson, J. M., Parker, D. C. (2000). Resting B Lymphocytes as APC for Naive T Lymphocytes: Dependence on CD40 Ligand/CD40. J. Immunol. 164: 688-697 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS