The Journal of Immunology, Vol 157, Issue 3 1062-1070, Copyright © 1996 by American Association of Immunologists

ARTICLES

Anergy-associated T cell antigen presentation. A mechanism of infectious tolerance in experimental autoimmune encephalomyelitis

MD Mannie, SK Rendall, PY Arnold, JP Nardella and GA White
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858, USA.

CD4+ T cells promote immune responses against foreign Ags while actively suppressing responses against self Ags. To address how CD4+ T cells ensure self-tolerance, we focused on two CD4+ T helper cells specific for myelin basic protein (MBP). GP2.E5/R1 T cells recognized rat MBP (RMBP) as a partial agonist and mediated mild experimental autoimmune encephalomyelitis (EAE), whereas R2 T cells recognized RMBP with full efficacy and mediated severe EAE. GP2.E5/R1 T cells were more susceptible to anergy induction than R2 T cells. Anergic GP2.E5/R1 T cells lacked proliferative reactivity, but expressed both I-A glycoproteins and high levels of radioresistant APC activity. During induction of anergy, these T cells acquired the ability to present MBP. In a separate subsequent culture without further addition of Ag, anergic GP2.E5/R1 T cells elicited full proliferative and IL-2 production responses by R2 T cells. Unlike activations induced via irradiated splenocytes, irradiated anergic T cells elicited anergy in R2 T cells in the form of a postactivational phase of nonresponsiveness. Anergic GP2.E5/R1 T cells not only transferred anergy to pathogenic R2 T cells in vitro, but these anergic T cells also transferred resistance to EAE in Lewis rats subsequently challenged with guinea pig MBP in CFA. Antagonistic signaling by autologous RMBP was more tolerogenic than that of guinea pig MBP in both in vitro and in vivo models of infectious anergy. We conclude that in the presence of tolerogenic mAb, antagonistic signaling by a self protein elicited the coordinate expression of anergy and T cell- mediated APC activity as a mechanism for the genesis and spread of infectious tolerance.

This article has been cited by other articles:

				M. D. Mannie and D. J. Abbott A Fusion Protein Consisting of IL-16 and the Encephalitogenic Peptide of Myelin Basic Protein Constitutes an Antigen-Specific Tolerogenic Vaccine That Inhibits Experimental Autoimmune Encephalomyelitis J. Immunol., August 1, 2007; 179(3): 1458 - 1465. [Abstract] [Full Text] [PDF]

				M. D. Mannie, B. A. Clayson, E. J. Buskirk, J. L. DeVine, J. J. Hernandez, and D. J. Abbott IL-2/Neuroantigen Fusion Proteins as Antigen-Specific Tolerogens in Experimental Autoimmune Encephalomyelitis (EAE): Correlation of T Cell-Mediated Antigen Presentation and Tolerance Induction J. Immunol., March 1, 2007; 178(5): 2835 - 2843. [Abstract] [Full Text] [PDF]

				D. Xia, S. Hao, and J. Xiang CD8+ Cytotoxic T-APC Stimulate Central Memory CD8+ T Cell Responses via Acquired Peptide-MHC Class I Complexes and CD80 Costimulation, and IL-2 Secretion. J. Immunol., September 1, 2006; 177(5): 2976 - 2984. [Abstract] [Full Text] [PDF]

				J. Xiang, H. Huang, and Y. Liu A New Dynamic Model of CD8+ T Effector Cell Responses via CD4+ T Helper-Antigen-Presenting Cells J. Immunol., June 15, 2005; 174(12): 7497 - 7505. [Abstract] [Full Text] [PDF]

				R. Kennedy, A. H. Undale, W. C. Kieper, M. S. Block, L. R. Pease, and E. Celis Direct Cross-Priming by Th Lymphocytes Generates Memory Cytotoxic T Cell Responses J. Immunol., April 1, 2005; 174(7): 3967 - 3977. [Abstract] [Full Text] [PDF]

				S. A. Wetzel, T. W. McKeithan, and D. C. Parker Peptide-Specific Intercellular Transfer of MHC Class II to CD4+ T Cells Directly from the Immunological Synapse upon Cellular Dissociation J. Immunol., January 1, 2005; 174(1): 80 - 89. [Abstract] [Full Text] [PDF]

				M. D. Mannie and M. R. Walker Feedback activation of T-cell antigen-presenting cells during interactions with T-cell responders J. Leukoc. Biol., August 1, 2001; 70(2): 252 - 260. [Abstract] [Full Text] [PDF]

				M. P. Reddy, C. A. S. Kinney, M. A. Chaikin, A. Payne, J. Fishman-Lobell, P. Tsui, P. R. Dal Monte, M. L. Doyle, M. R. Brigham-Burke, D. Anderson, et al. Elimination of Fc Receptor-Dependent Effector Functions of a Modified IgG4 Monoclonal Antibody to Human CD4 J. Immunol., February 15, 2000; 164(4): 1925 - 1933. [Abstract] [Full Text] [PDF]

				D. M. Patel, P. Y. Arnold, G. A. White, J. P. Nardella, and M. D. Mannie Class II MHC/Peptide Complexes Are Released from APC and Are Acquired by T Cell Responders During Specific Antigen Recognition J. Immunol., November 15, 1999; 163(10): 5201 - 5210. [Abstract] [Full Text] [PDF]

				L. Clark, L. Otvos Jr., P. L. Stein, X.-M. Zhang, A. F. Skorupa, G. E. Lesh, F. A. McMorris, and E. Heber-Katz Golli-Induced Paralysis: A Study in Anergy and Disease J. Immunol., April 1, 1999; 162(7): 4300 - 4310. [Abstract] [Full Text] [PDF]

				L. S. Taams, W. van Eden, and M. H. M. Wauben Dose-Dependent Induction of Distinct Anergic Phenotypes: Multiple Levels of T Cell Anergy J. Immunol., February 15, 1999; 162(4): 1974 - 1981. [Abstract] [Full Text] [PDF]