RTL551 treatment of EAE reduces CD226 and T-bet+ CD4 T cells in periphery and prevents infiltration of T-bet+ IL-17, IFN-γ producing T cells into CNS

PLoS ONE

Volumn 6, Issue 7, 2011, Pages

  Sinha, Sushmita ^a,b   Miller, Lisa M ^a,b   Subramanian, Sandhya ^a   Burrows, Gregory G ^b,c   Vandenbark, Arthur A ^a,b   Offner, Halina ^a,b  

^a PORTLAND VA MEDICAL CENTER   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; CD226 ANTIGEN; CELL SURFACE MARKER; DRUG VEHICLE; GAMMA INTERFERON; HERMES ANTIGEN; IMMUNOMODULATING AGENT; INTERLEUKIN 13; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 6; LYMPHOCYTE SURFACE MARKER; RECOMBINANT T LYMPHOCYTE RECEPTOR LIGAND 550; RECOMBINANT T LYMPHOCYTE RECEPTOR LIGAND 551; TRANSCRIPTION FACTOR T BET; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CD4 ANTIGEN; HYBRID PROTEIN; RTL551 PROTEIN; T BOX TRANSCRIPTION FACTOR; T BOX TRANSCRIPTION FACTOR TBX21; T-BOX TRANSCRIPTION FACTOR TBX21;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN BINDING; ARTICLE; CD4+ T LYMPHOCYTE; CELL EXPANSION; CELL INFILTRATION; CELL MIGRATION; CONTROLLED STUDY; CYTOKINE RELEASE; CYTOKINE RESPONSE; EFFECTOR CELL; EX VIVO STUDY; IMMUNOPHENOTYPING; MALE; MOUSE; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; SITE DIRECTED MUTAGENESIS; SPLEEN CELL; AMINO ACID SEQUENCE; ANIMAL; C57BL MOUSE; CELL MOTION; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; DOWN REGULATION; DRUG EFFECT; FLOW CYTOMETRY; IMMUNOLOGY; INFLAMMATION; METABOLISM; MOLECULAR GENETICS; T LYMPHOCYTE; TIME; TREATMENT OUTCOME;

MUS;

AMINO ACID SEQUENCE; ANIMALS; ANTIGENS, CD4; CD4-POSITIVE T-LYMPHOCYTES; CELL MOVEMENT; CELL PROLIFERATION; CENTRAL NERVOUS SYSTEM; DOWN-REGULATION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FLOW CYTOMETRY; INFLAMMATION; INTERFERON-GAMMA; INTERLEUKIN-17; MALE; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; RECOMBINANT FUSION PROTEINS; T-BOX DOMAIN PROTEINS; T-LYMPHOCYTES; TIME FACTORS; TREATMENT OUTCOME;

EID: 79959996770     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0021868     Document Type: Article

References (32)

1. Offner H, Sinha S, Wang C, Burrows GG, Vandenbark AA, (2008) Recombinant T cell receptor ligands: immunomodulatory, neuroprotective and neuroregenerative effects suggest application as therapy for multiple sclerosis. Rev Neurosci 19: 327-339.
2. Sinha S, Subramanian S, Emerson-Webber A, Lindner M, Burrows GG, et al. (2010) Recombinant TCR Ligand Reverses Clinical Signs and CNS Damage of EAE Induced by Recombinant Human MOG. J Neuroimmune Pharmacol 5: 231-239.
3. Sinha S, Subramanian S, Proctor TM, Kaler LJ, Grafe M, et al. (2007) A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS. J Neurosci 27: 12531-12539.
4. Sinha S, Subramanian S, Miller L, Proctor TM, Roberts C, et al. (2009) Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand. J Neurosci 29: 3816-3823.
5. Sinha S, Miller L, Subramanian S, McCarty OJ, Proctor T, et al. (2010) Binding of recombinant T cell receptor ligands (RTL) to antigen presenting cells prevents upregulation of CD11b and inhibits T cell activation and transfer of experimental autoimmune encephalomyelitis. J Neuroimmunol 225: 52-61.
6. Burrows GG, Chou YK, Wang C, Chang JW, Finn TP, et al. (2001) Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells. J Immunol 167: 4386-4395.
7. Wang C, Mooney JL, Meza-Romero R, Chou YK, Huan J, et al. (2003) Recombinant TCR ligand induces early TCR signaling and a unique pattern of downstream activation. J Immunol 171: 1934-1940.
8. Swanborg RH, (1995) Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease. Clin Immunol Immunopathol 77: 4-13.
9. Burrows GG, Chang JW, Bachinger HP, Bourdette DN, Offner H, et al. (1999) Design, engineering and production of functional single-chain T cell receptor ligands. Protein Eng 12: 771-778.
10. Fontenot AP, Keizer TS, McCleskey M, Mack DG, Meza-Romero R, et al. (2006) Recombinant HLA-DP2 binds beryllium and tolerizes beryllium-specific pathogenic CD4+ T cells. J Immunol 177: 3874-3883.
11. Bebo BF Jr, Vandenbark AA, Offner H, (1996) Male SJL mice do not relapse after induction of EAE with PLP 139-151. J Neurosci Res 45: 680-689.
12. Offner H, Buenafe AC, Vainiene M, Celnik B, Weinberg AD, et al. (1993) Where, when, and how to detect biased expression of disease-relevant V beta genes in rats with experimental autoimmune encephalomyelitis. J Immunol 151: 506-517.
13. Chu CQ, Wittmer S, Dalton DK, (2000) Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J Exp Med 192: 123-128.
14. Siffrin V, Radbruch H, Glumm R, Niesner R, Paterka M, et al. (2010) In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33: 424-436.
15. Huan J, Subramanian S, Jones R, Rich C, Link J, et al. (2004) Monomeric recombinant TCR ligand reduces relapse rate and severity of experimental autoimmune encephalomyelitis in SJL/J mice through cytokine switch. J Immunol 172: 4556-4566.
16. Offner H, Subramanian S, Wang C, Afentoulis M, Vandenbark AA, et al. (2005) Treatment of passive experimental autoimmune encephalomyelitis in SJL mice with a recombinant TCR ligand induces IL-13 and prevents axonal injury. J Immunol 175: 4103-4111.
17. Vandenbark AA, Rich C, Mooney J, Zamora A, Wang C, et al. (2003) Recombinant TCR ligand induces tolerance to myelin oligodendrocyte glycoprotein 35-55 peptide and reverses clinical and histological signs of chronic experimental autoimmune encephalomyelitis in HLA-DR2 transgenic mice. J Immunol 171: 127-133.
18. Dardalhon V, Schubart AS, Reddy J, Meyers JH, Monney L, et al. (2005) CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol 175: 1558-1565.
19. Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, et al. (2009) CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun 10: 5-10.
20. Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, et al. (1996) DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4: 573-581.
21. Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, et al. (1999) Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity 11: 615-623.
22. Tamura T, Igarashi O, Hino A, Yamane H, Aizawa S, et al. (2001) Impairment in the expression and activity of Fyn during differentiation of naive CD4+ T cells into the Th2 subset. J Immunol 167: 1962-1969.
23. Tamura T, Nakano H, Nagase H, Morokata T, Igarashi O, et al. (1995) Early activation signal transduction pathways of Th1 and Th2 cell clones stimulated with anti-CD3. Roles of protein tyrosine kinases in the signal for IL-2 and IL-4 production. J Immunol 155: 4692-4701.
24. Shibuya K, Shirakawa J, Kameyama T, Honda S, Tahara-Hanaoka S, et al. (2003) CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med 198: 1829-1839.
25. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, et al. (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
26. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, et al. (2004) Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 200: 79-87.
27. Lovett-Racke AE, Rocchini AE, Choy J, Northrop SC, Hussain RZ, et al. (2004) Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity 21: 719-731.
28. Nath N, Prasad R, Giri S, Singh AK, Singh I, (2006) T-bet is essential for the progression of experimental autoimmune encephalomyelitis. Immunology 118: 384-391.
29. Frisullo G, Angelucci F, Caggiula M, Nociti V, Iorio R, et al. (2006) pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity. J Neurosci Res 84: 1027-1036.
30. Pure E, Cuff CA, (2001) A crucial role for CD44 in inflammation. Trends Mol Med 7: 213-221.
31. Yang Y, Weiner J, Liu Y, Smith AJ, Huss DJ, et al. (2009) T-bet is essential for encephalitogenicity of both Th1 and Th17 cells. J Exp Med 206: 1549-1564.
32. Gocke AR, Cravens PD, Ben LH, Hussain RZ, Northrop SC, et al. (2007) T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. pp. 1341-1348.