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PLOS ONE  2013 

A Novel Epitope from CD22 Regulates Th1 and Th17 Cell Function in Systemic Lupus Erythematosus

DOI: 10.1371/journal.pone.0064572

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Abstract:

The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4+ T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4+ T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4+ T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4+ T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4+ T cells. Moreover, the expression of CD45RO on CD4+ T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.

References

[1]  Rahman A, Isenberg DA (2008) Systemic lupus erythematosus. N Engl J Med 358: 929–939.
[2]  Lipsky PE (2001) Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2: 764–766.
[3]  Robak E, Robak T (2009) Monoclonal antibodies in the treatment of systemic lupus erythematosus. Curr Drug Targets 10: 26–37.
[4]  Schulte RJ, Campbell MA, Fischer WH, Sefton BM (1992) Tyrosine phosphorylation of CD22 during B cell activation. Science 258: 1001–1004.
[5]  Carnahan J, Wang P, Kendall R, Chen C, Hu S, et al. (2003) Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res 9: 3982S–3990S.
[6]  D?rner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, et al. (2006) Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther 8: R74.
[7]  Law CL, Aruffo A, Chandran KA, Doty RT, Clark EA (1995) Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind multiple sialylated ligands expressed on B and T cells. J Immunol 155: 3368–376.
[8]  Tuscano J, Engel P, Tedder TF, Kehrl JH (1996) Engagement of the adhesion receptor CD22 triggers a potent stimulatory signal for B cells and blocking CD22/CD22L interactions impairs T-cell proliferation. Blood 87: 4723–4730.
[9]  Haas KM, Sen S, Sanford IG, Miller AS, Poe JC, et al. (2006) CD22 ligand binding regulates normal and malignant B lymphocyte survival in vivo. J Immunol 177: 3063–3073.
[10]  Heimberger AB, Crotty LE, Archer GE, Hess KR, Wikstrand CJ, et al. (2003) Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res 9: 4247–4254.
[11]  Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D (1994) The role of B cells in lpr/lpr-induced autoimmunity. J Exp Med 180: 1295–1306.
[12]  Blomqvist SR, Vidarsson H, Fitzgerald S, Johansson BR, Ollerstam A, et al. (2004) Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1. J Clin Invest 113: 1560–1570.
[13]  Smith KM, Pottage L, Thomas ER, Leishman AJ, Doig TN, et al. (2000) Th1 and Th2 CD4+ T cells provide help for B cell clonal expansion and antibody synthesis in a similar manner in vivo. J Immunol 165: 3136–3144.
[14]  Hsu HC, Yang P, Wang J, Wu Q, Myers R, et al. (2008) Interleukin 17-producing T helper cells and interleukin-17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9: 166–175.
[15]  Lim HW, Hillsamer P, Banham AH, Kim CH (2005) Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol 175: 4180–4183.
[16]  Mitsdoerffer M, Lee Y, J?ger A, Kim HJ, Korn T, et al. (2010) Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci U S A 107: 14292–14297.
[17]  Smith KM, Brewer JM, Rush CM, Riley J, Garside P (2004) In vivo generated Th1 cells can migrate to B cell follicles to support B cell responses. J Immunol 173: 1640–1646.
[18]  Yuan J, Cao AL, Yu M, Lin QW, Yu X, et al. (2010) Th17 cells facilitate the humoral immune response in patients with acute viral myocarditis. J Clin Immunol 30: 226–234.
[19]  Yuan J, Yu M, Lin QW, Cao AL, Yu X, et al. (2010) Neutralization of IL-17 inhibits the production of anti-ANT autoantibodies in CVB3-induced acute viral myocarditis. Int Immunopharmacol 10: 272–276.
[20]  Sgroi D, Koretzky GA, Stamenkovic I (1995) Regulation of CD45 engagement by the B-cell receptor CD22. Proc Natl Acad Sci U S A 92: 4026–4030.
[21]  Aruffo A, Kanner SB, Sgroi D, Ledbetter JA, Stamenkovic I (1992) CD22-mediated stimulation of T cells regulates T-cell receptor/CD3-induced signaling. Proc Natl Acad Sci U S A 89: 10242–10246.
[22]  Zhu J, Paul WE (2010) Heterogeneity and plasticity of T helper cells. Cell Res 20: 4–12.

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