Immune Therapy for Autoimmune Diseases

Lawrence Steinman

Abstract: Our increasing understanding of the pathophysiology of autoimmune disease has revealed a number of checkpoints that can be targeted with immune therapy, including key mediators of lymphocyte adhesion and migration, destructive cytokines involved in tissue damage, and the complex of molecules critical in the presentation of self-antigen and the activation of autoaggressive T lymphocytes. In many organ-specific autoimmune diseases, the identity of the molecules attacked by T cells and autoantibodies is known and attempts are under way to tolerize the immune system with a high level of specificity to these targets.

Department of Neurological Sciences and Neurology, and Interdepartmental Program in Immunology, Stanford University, Stanford, CA 94305, USA.

E-mail: steinman{at}stanford.edu

Improvement of Psoriasis after Tonsillectomy Is Associated with a Decrease in the Frequency of Circulating T Cells That Recognize Streptococcal Determinants and Homologous Skin Determinants.

R. H. Thorleifsdottir, S. L. Sigurdardottir, B. Sigurgeirsson, J. H. Olafsson, M. I. Sigurdsson, H. Petersen, S. Arnadottir, J. E. Gudjonsson, A. Johnston, and H. Valdimarsson (2012)
J. Immunol. 188, 5160-5165
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Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis.

S. Kimball, R. Vieth, H.-M. Dosch, A. Bar-Or, R. Cheung, D. Gagne, P. O'Connor, C. D'Souza, M. Ursell, and J. M. Burton (2011)
J. Clin. Endocrinol. Metab. 96, 2826-2834
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Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain.

L. Steinman (2010)
PNAS 107, 20595-20596
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In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance.

A. Annoni, B. D. Brown, A. Cantore, L. S. Sergi, L. Naldini, and M.-G. Roncarolo (2009)
Blood 114, 5152-5161
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Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation.

M. Kneilling, R. Mailhammer, L. Hultner, T. Schonberger, K. Fuchs, M. Schaller, D. Bukala, S. Massberg, C. A. Sander, H. Braumuller, et al. (2009)
Blood 114, 1696-1706
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Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells.

M. Wigren, D. Bengtsson, P. Duner, K. Olofsson, H. Bjorkbacka, E. Bengtsson, G. N. Fredrikson, and J. Nilsson (2009)
Circ. Res. 104, e62-e70
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Anti-Ccl2 Spiegelmer Permits 75% Dose Reduction of Cyclophosphamide to Control Diffuse Proliferative Lupus Nephritis and Pneumonitis in MRL-Fas(lpr) Mice.

O. Kulkarni, D. Eulberg, N. Selve, S. Zollner, R. Allam, R. D. Pawar, S. Pfeiffer, S. Segerer, S. Klussmann, and H.-J. Anders (2009)
J. Pharmacol. Exp. Ther. 328, 371-377
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Mitomycin C-treated dendritic cells inactivate autoreactive T cells: Toward the development of a tolerogenic vaccine in autoimmune diseases.

P. Terness, T. Oelert, S. Ehser, J. J. Chuang, I. Lahdou, C. Kleist, F. Velten, G. J. Hammerling, B. Arnold, and G. Opelz (2008)
PNAS 105, 18442-18447
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Shedded neuronal ICAM-5 suppresses T-cell activation.

L. Tian, J. Lappalainen, M. Autero, S. Hanninen, H. Rauvala, and C. G. Gahmberg (2008)
Blood 111, 3615-3625
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Spiegelmer Inhibition of CCL2/MCP-1 Ameliorates Lupus Nephritis in MRL-(Fas)lpr Mice.

O. Kulkarni, R. D. Pawar, W. Purschke, D. Eulberg, N. Selve, K. Buchner, V. Ninichuk, S. Segerer, V. Vielhauer, S. Klussmann, et al. (2007)
J. Am. Soc. Nephrol. 18, 2350-2358
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Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study.

W. de Jager, E. P A H Hoppenreijs, N. M Wulffraat, L. R Wedderburn, W. Kuis, and B. J Prakken (2007)
Ann Rheum Dis 66, 589-598
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Increased Frequencies of Cochlin-Specific T Cells in Patients with Autoimmune Sensorineural Hearing Loss.

M.-J. Baek, H.-M. Park, J. M. Johnson, C. Z. Altuntas, D. Jane-wit, R. Jaini, C. A. Solares, D. M. Thomas, E. J. Ball, N. G. Robertson, et al. (2006)
J. Immunol. 177, 4203-4210
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Controlling autoimmunity in sporadic inclusion-body myositis.

L. Steinman (2006)
Neurology 66, S56-S58
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Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite.

M. Platten, P. P. Ho, S. Youssef, P. Fontoura, H. Garren, E. M. Hur, R. Gupta, L. Y. Lee, B. A. Kidd, W. H. Robinson, et al. (2005)
Science 310, 850-855
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A Suppressive Oligodeoxynucleotide Enhances the Efficacy of Myelin Cocktail/IL-4-Tolerizing DNA Vaccination and Treats Autoimmune Disease.

P. P. Ho, P. Fontoura, M. Platten, R. A. Sobel, J. J. DeVoss, L. Y. Lee, B. A. Kidd, B. H. Tomooka, J. Capers, A. Agrawal, et al. (2005)
J. Immunol. 175, 6226-6234
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NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.

C. Semino, G. Angelini, A. Poggi, and A. Rubartelli (2005)
Blood 106, 609-616
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Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences.

R. D. Stout, C. Jiang, B. Matta, I. Tietzel, S. K. Watkins, and J. Suttles (2005)
J. Immunol. 175, 342-349
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Modulation of Memory CD4 T Cell Function and Survival Potential by Altering the Strength of the Recall Stimulus.

D. S. Patke and D. L. Farber (2005)
J. Immunol. 174, 5433-5443
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