Original Article

Requirements for Bone Marrow–derived Antigen-presenting Cells in Priming Cytotoxic T Cell Responses to Intracellular Pathogens

Correspondence to: Michael J. Bevan, Department of Immunology and Howard Hughes Medical Institute, School of Medicine, Box 357370, University of Washington, Seattle, WA 98195. Tel:206-685-3610 Fax:206-685-3612

Bone marrow (BM)-derived antigen-presenting cells (APCs) are potent stimulators of T cell immune responses. We investigated the requirements for antigen presentation by these cells in priming cytotoxic T lymphocyte (CTL) responses to intracellular bacterial and viral pathogens. [ParentF₁] radiation BM chimeras were constructed using C57BL/6 donors and (C57BL/6 x BALB/c)F₁ recipients. Infection of chimeric mice with either Listeria monocytogenes or vaccinia virus expressing the nucleoprotein (NP) antigen from lymphocytic choriomeningitis virus (LCMV) primed H2-D^b–restricted, but not H2-K^d–restricted CTL responses, demonstrating the requirement for BM-derived APCs for successful priming of CTL responses to these pathogens. Surprisingly, this did not hold true for chimeric mice infected with LCMV itself. LCMV-infected animals developed strong CTL responses specific for both H2-D^b– and H2-L^d–restricted NP epitopes. These findings indicate that in vivo priming of CTL responses to LCMV is remarkably insensitive to deficiencies in antigen presentation by professional BM-derived APCs.

Key Words: cross-presentation, cytotoxic T cell, bacterial immunity, viral immunity, radiation chimera

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

This article has been cited by other articles:

• Dzierszinski, F., Pepper, M., Stumhofer, J. S., LaRosa, D. F., Wilson, E. H., Turka, L. A., Halonen, S. K., Hunter, C. A., Roos, D. S. (2007). Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells. Infect. Immun. 75: 5200-5209 [Abstract] [Full Text]  
• Gasteiger, G., Kastenmuller, W., Ljapoci, R., Sutter, G., Drexler, I. (2007). Cross-Priming of Cytotoxic T Cells Dictates Antigen Requisites for Modified Vaccinia Virus Ankara Vector Vaccines. J. Virol. 81: 11925-11936 [Abstract] [Full Text]  
• Hagymasi, A. T., Slaiby, A. M., Mihalyo, M. A., Qui, H. Z., Zammit, D. J., Lefrancois, L., Adler, A. J. (2007). Steady State Dendritic Cells Present Parenchymal Self-Antigen and Contribute to, but Are Not Essential for, Tolerization of Naive and Th1 Effector CD4 Cells. J. Immunol. 179: 1524-1531 [Abstract] [Full Text]  
• Thomas, S., Kolumam, G. A., Murali-Krishna, K. (2007). Antigen Presentation by Nonhemopoietic Cells Amplifies Clonal Expansion of Effector CD8 T Cells in a Pathogen-Specific Manner. J. Immunol. 178: 5802-5811 [Abstract] [Full Text]  
• Belz, G. T., Shortman, K., Bevan, M. J., Heath, W. R. (2005). CD8{alpha}+ Dendritic Cells Selectively Present MHC Class I-Restricted Noncytolytic Viral and Intracellular Bacterial Antigens In Vivo. J. Immunol. 175: 196-200 [Abstract] [Full Text]  
• Cusi, M. G., Del Vecchio, M. T., Terrosi, C., Savellini, G. G., Di Genova, G., La Placa, M., Fallarino, F., Moser, C., Cardone, C., Giorgi, G., Francini, G., Correale, P. (2005). Immune-Reconstituted Influenza Virosome Containing CD40L Gene Enhances the Immunological and Protective Activity of a Carcinoembryonic Antigen Anticancer Vaccine. J. Immunol. 174: 7210-7216 [Abstract] [Full Text]  
• Kursar, M., Hopken, U. E., Koch, M., Kohler, A., Lipp, M., Kaufmann, S. H.E., Mittrucker, H.-W. (2005). Differential requirements for the chemokine receptor CCR7 in T cell activation during Listeria monocytogenes infection. JEM 201: 1447-1457 [Abstract] [Full Text]  
• Probst, H. C., van den Broek, M. (2005). Priming of CTLs by Lymphocytic Choriomeningitis Virus Depends on Dendritic Cells. J. Immunol. 174: 3920-3924 [Abstract] [Full Text]  
• Kerksiek, K. M., Niedergang, F., Chavrier, P., Busch, D. H., Brocker, T. (2005). Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo. Blood 105: 742-749 [Abstract] [Full Text]  
• Steele, L. N., Balsara, Z. R., Starnbach, M. N. (2004). Hematopoietic Cells Are Required to Initiate a Chlamydia trachomatis-Specific CD8+ T Cell Response. J. Immunol. 173: 6327-6337 [Abstract] [Full Text]  
• Serna, A., Ramirez, M. C., Soukhanova, A., Sigal, L. J. (2003). Cutting Edge: Efficient MHC Class I Cross-Presentation during Early Vaccinia Infection Requires the Transfer of Proteasomal Intermediates between Antigen Donor and Presenting Cells. J. Immunol. 171: 5668-5672 [Abstract] [Full Text]  
• Schuler, T., Blankenstein, T. (2003). Cutting Edge: CD8+ Effector T Cells Reject Tumors by Direct Antigen Recognition but Indirect Action on Host Cells. J. Immunol. 170: 4427-4431 [Abstract] [Full Text]  
• Huang, C.-T., Huso, D. L., Lu, Z., Wang, T., Zhou, G., Kennedy, E. P., Drake, C. G., Morgan, D. J., Sherman, L. A., Higgins, A. D., Pardoll, D. M., Adler, A. J. (2003). CD4+ T Cells Pass Through an Effector Phase During the Process of In Vivo Tolerance Induction. J. Immunol. 170: 3945-3953 [Abstract] [Full Text]  
• Solomayer, E.-F., Feuerer, M., Bai, L., Umansky, V., Beckhove, P., Meyberg, G. C., Bastert, G., Schirrmacher, V., Diel, I. J. (2003). Influence of Adjuvant Hormone Therapy and Chemotherapy on the Immune System Analysed in the Bone Marrow of Patients with Breast Cancer. Clin. Cancer Res. 9: 174-180 [Abstract] [Full Text]  
• Ramirez, M. C., Sigal, L. J. (2002). Macrophages and Dendritic Cells Use the Cytosolic Pathway to Rapidly Cross-Present Antigen from Live, Vaccinia-Infected Cells. J. Immunol. 169: 6733-6742 [Abstract] [Full Text]  
• Prilliman, K. R., Lemmens, E. E., Palioungas, G., Wolfe, T. G., Allison, J. P., Sharpe, A. H., Schoenberger, S. P. (2002). Cutting Edge: A Crucial Role for B7-CD28 in Transmitting T Help from APC to CTL. J. Immunol. 169: 4094-4097 [Abstract] [Full Text]  
• den Haan, J. M.M., Bevan, M. J. (2002). Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8- Dendritic Cells In Vivo. JEM 196: 817-827 [Abstract] [Full Text]  
• Pasetti, M. F., Salerno-Goncalves, R., Sztein, M. B. (2002). Salmonella enterica Serovar Typhi Live Vector Vaccines Delivered Intranasally Elicit Regional and Systemic Specific CD8+ Major Histocompatibility Class I-Restricted Cytotoxic T Lymphocytes. Infect. Immun. 70: 4009-4018 [Abstract] [Full Text]  
• Higgins, A. D., Mihalyo, M. A., McGary, P. W., Adler, A. J. (2002). CD4 Cell Priming and Tolerization Are Differentially Programmed by APCs upon Initial Engagement. J. Immunol. 168: 5573-5581 [Abstract] [Full Text]  
• Skoberne, M., Geginat, G. (2002). Efficient In Vivo Presentation of Listeria monocytogenes- Derived CD4 and CD8 T Cell Epitopes in the Absence of IFN-{gamma}. J. Immunol. 168: 1854-1860 [Abstract] [Full Text]  
• Cho, J. H., Youn, J. W., Sung, Y. C. (2001). Cross-Priming as a Predominant Mechanism for Inducing CD8+ T Cell Responses in Gene Gun DNA Immunization. J. Immunol. 167: 5549-5557 [Abstract] [Full Text]  
• Williams, M. A., Tan, J. T., Adams, A. B., Durham, M. M., Shirasugi, N., Whitmire, J. K., Harrington, L. E., Ahmed, R., Pearson, T. C., Larsen, C. P. (2001). Characterization of Virus-Mediated Inhibition of Mixed Chimerism and Allospecific Tolerance. J. Immunol. 167: 4987-4995 [Abstract] [Full Text]  
• Bai, X.-F., Gao, J.-X., Liu, J., Wen, J., Zheng, P., Liu, Y. (2001). On the Site and Mode of Antigen Presentation for the Initiation of Clonal Expansion of CD8 T Cells Specific for a Natural Tumor Antigen. Cancer Res. 61: 6860-6867 [Abstract] [Full Text]  
• den Haan, J. M.M., Lehar, S. M., Bevan, M. J. (2000). CD8+ but Not CD8- Dendritic Cells Cross-prime Cytotoxic T Cells In Vivo. JEM 192: 1685-1696 [Abstract] [Full Text]  
• Sigal, L. J., Rock, K. L. (2000). Bone Marrow-derived Antigen-presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (TAP)-dependent and -independent Pathways of Antigen Presentation. JEM 192: 1143-1150 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS