Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody - PubMed (original) (raw)
doi: 10.2337/db06-1632. Epub 2007 Apr 24.
Affiliations
- PMID: 17456848
- DOI: 10.2337/db06-1632
Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody
Hiroki Ishikawa et al. Diabetes. 2007 Aug.
Abstract
Anti-CD3 monoclonal antibody (mAb) has been shown to induce tolerance and to be an effective treatment for diabetes both in animal models and in human trials. We have shown that anti-CD3 mAb given orally is biologically active in the gut and suppresses experimental autoimmune encephalitis by the induction of a regulatory T-cell that expresses latency-associated peptide (LAP) on its surface. In the present study, we investigated the effect of oral anti-CD3 mAb on the prevention of autoimmune diabetes in AKR mice in which the low-dose streptozocin (STZ) model induces autoimmunity to the beta-cells of the islets. We found that oral anti-CD3 mAb given at doses of 50 and 250 microg/feeding suppressed the incidence of diabetes in this model with the best effects seen at the 50 microg/dose. Associated with suppression, we observed decreased cell proliferation in the spleen and conversion of T-helper (Th)1 responses into Th2/Th3 responses in the periphery, including the pancreatic lymph nodes. Oral anti-CD3 mAb increased the expression of LAP on CD4(+) T-cells, and these cells could adoptively transfer protection. Protection by oral anti-CD3 was transforming growth factor-beta dependent. Our results demonstrate that oral anti-CD3 is effective in the model of STZ-induced diabetes and may be a useful form of therapy for type 1 diabetes in humans.
Similar articles
- Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells.
Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, Wu H, Chen ML, Gandhi R, Miller A, Maron R, Weiner HL. Ochi H, et al. Nat Med. 2006 Jun;12(6):627-35. doi: 10.1038/nm1408. Epub 2006 May 21. Nat Med. 2006. PMID: 16715091 - Oral anti-CD3 antibody treatment induces regulatory T cells and inhibits the development of atherosclerosis in mice.
Sasaki N, Yamashita T, Takeda M, Shinohara M, Nakajima K, Tawa H, Usui T, Hirata K. Sasaki N, et al. Circulation. 2009 Nov 17;120(20):1996-2005. doi: 10.1161/CIRCULATIONAHA.109.863431. Epub 2009 Nov 2. Circulation. 2009. PMID: 19884470 - CD3 antibody treatment stimulates the functional capability of regulatory T cells.
Chatenoud L. Chatenoud L. Novartis Found Symp. 2003;252:279-86; discussion 286-90. Novartis Found Symp. 2003. PMID: 14609225 Review. - Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment.
You S, Leforban B, Garcia C, Bach JF, Bluestone JA, Chatenoud L. You S, et al. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6335-40. doi: 10.1073/pnas.0701171104. Epub 2007 Mar 26. Proc Natl Acad Sci U S A. 2007. PMID: 17389382 Free PMC article. - Achieving antigen-specific tolerance in diabetes: regulating specifically.
Chen W, Bluestone JA, Herold KC. Chen W, et al. Int Rev Immunol. 2005 Sep-Dec;24(5-6):287-305. doi: 10.1080/08830180500379671. Int Rev Immunol. 2005. PMID: 16318983 Review.
Cited by
- Insulin-Dependent Maturation of Newly Generated Olfactory Sensory Neurons after Injury.
Kuboki A, Kikuta S, Otori N, Kojima H, Matsumoto I, Reisert J, Yamasoba T. Kuboki A, et al. eNeuro. 2021 May 19;8(3):ENEURO.0168-21.2021. doi: 10.1523/ENEURO.0168-21.2021. Print 2021 May-Jun. eNeuro. 2021. PMID: 33906971 Free PMC article. - Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse model transgenic for the CD3 epsilon chain.
Kuhn C, Rezende RM, da Cunha AP, Valette F, Quintana FJ, Chatenoud L, Weiner HL. Kuhn C, et al. J Autoimmun. 2017 Jan;76:115-122. doi: 10.1016/j.jaut.2016.10.001. Epub 2016 Oct 10. J Autoimmun. 2017. PMID: 27745778 Free PMC article. - LAP+CD4+ T cells are elevated among the peripheral blood mononuclear cells and tumor tissue of patients with hepatocellular carcinoma.
Ou X, Guan J, Chen JS, Ying JC, Liu XP, Tian PK, Liu JK, Nie LP, Zhao Y, Yu GY. Ou X, et al. Exp Ther Med. 2018 Aug;16(2):788-796. doi: 10.3892/etm.2018.6229. Epub 2018 May 29. Exp Ther Med. 2018. PMID: 30116333 Free PMC article. - Effect of intestinal microbiota on the induction of regulatory CD25+ CD4+ T cells.
Ishikawa H, Tanaka K, Maeda Y, Aiba Y, Hata A, Tsuji NM, Koga Y, Matsumoto T. Ishikawa H, et al. Clin Exp Immunol. 2008 Jul;153(1):127-35. doi: 10.1111/j.1365-2249.2008.03668.x. Epub 2008 May 5. Clin Exp Immunol. 2008. PMID: 18460018 Free PMC article. - Inducible CD4+LAP+Foxp3- regulatory T cells suppress allergic inflammation.
Duan W, So T, Mehta AK, Choi H, Croft M. Duan W, et al. J Immunol. 2011 Dec 15;187(12):6499-507. doi: 10.4049/jimmunol.1101398. Epub 2011 Nov 11. J Immunol. 2011. PMID: 22079987 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials