CD4+CD25+CD127hi cell frequency predicts disease progression in type 1 diabetes

Abstract

Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain β cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, β cell survival, and response to antiinflammatory immunotherapy.J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S87-97. (PMID: 12894131); Blood. 1995 Oct 1;86(7):2672-8. (PMID: 7545465); Exp Clin Endocrinol Diabetes. 2007 Jan;115(1):33-7. (PMID: 17286232); J Am Acad Dermatol. 2003 Nov;49(5):816-25. (PMID: 14576659); Semin Immunol. 2012 Jun;24(3):209-17. (PMID: 22551764); Diabetes. 2015 Jan;64(1):172-82. (PMID: 25157096); Data Brief. 2016 Aug 06;8:1348-51. (PMID: 27579340); Immunity. 1998 Nov;9(5):745-55. (PMID: 9846495); J Exp Med. 1994 Feb 1;179(2):493-502. (PMID: 7905018); Lancet. 2014 Jan 4;383(9911):69-82. (PMID: 23890997); Nat Med. 2016 Dec;22(12):1482-1487. (PMID: 27798614); Proc Natl Acad Sci U S A. 2011 May 10;108(19):7938-43. (PMID: 21518860); Int Immunol. 2016 Apr;28(4):163-71. (PMID: 26874355); Biochim Biophys Acta. 2011 May;1813(5):878-88. (PMID: 21296109); J Drugs Dermatol. 2003 Dec;2(6):624-8. (PMID: 14711140); Nat Immunol. 2005 Nov;6(11):1133-41. (PMID: 16200068); Clin Ther. 2016 Jun;38(6):1327-1339. (PMID: 27209482); Nat Rev Immunol. 2016 Feb;16(2):90-101. (PMID: 26688349); Cell. 1994 Jan 28;76(2):241-51. (PMID: 7904900); Med Sci Monit. 2018 Aug 28;24:5996-6001. (PMID: 30153246); J Exp Med. 1995 Nov 1;182(5):1527-36. (PMID: 7595222); Immunology. 1999 Feb;96(2):155-63. (PMID: 10233690); J Diabetes Complications. 2015 Nov-Dec;29(8):1105-11. (PMID: 26427560); Diabetes Metab Res Rev. 2006 May-Jun;22(3):184-9. (PMID: 16222648); J Clin Invest. 2001 Nov;108(9):1331-9. (PMID: 11696578); J Biol Chem. 1997 Aug 22;272(34):21597-603. (PMID: 9261181); J Transl Med. 2007 Jun 07;5:27. (PMID: 17555598); Acta Clin Belg. 1993;48(2):86-95. (PMID: 8392249); Clin Exp Immunol. 2006 Sep;145(3):480-4. (PMID: 16907917); Diabetes Care. 2013 Nov;36(11):3454-9. (PMID: 23990516); Immunity. 1998 Mar;8(3):275-83. (PMID: 9529145); J Pediatr Endocrinol Metab. 2001 Apr;14(4):435-41. (PMID: 11327378); J Pediatr Endocrinol Metab. 2001 Nov-Dec;14(9):1585-96. (PMID: 11795651); Nature. 1996 Oct 31;383(6603):787-93. (PMID: 8893001); Clin Immunol. 2016 May;166-167:72-80. (PMID: 27114212); Diabetes. 2005 Jun;54(6):1763-9. (PMID: 15919798); Diabetes Care. 2003 Mar;26(3):832-6. (PMID: 12610045); Lancet Diabetes Endocrinol. 2013 Dec;1(4):284-94. (PMID: 24622414); Diabetes Nutr Metab. 2002 Aug;15(4):246-51. (PMID: 12416662); Clin Exp Immunol. 2007 Oct;150(1):75-82. (PMID: 17711492); Pediatr Diabetes. 2019 May;20(3):286-292. (PMID: 30714298); J Immunol. 2009 Aug 15;183(4):2232-41. (PMID: 19635906); J Immunol. 1994 Aug 15;153(4):1707-13. (PMID: 7913944); PLoS One. 2017 May 1;12(5):e0176860. (PMID: 28459844); Diabetes. 2008 Apr;57(4):929-37. (PMID: 18299313); Clin Exp Immunol. 2016 Jan;183(1):16-29. (PMID: 26102289); J Leukoc Biol. 2009 Feb;85(2):251-61. (PMID: 18955544); Arch Dis Child. 1999 Apr;80(4):367-9. (PMID: 10086946); Horm Res Paediatr. 2013;80(4):287-92. (PMID: 24051686); J Immunol. 2007 Jul 15;179(2):744-7. (PMID: 17617562); J Clin Endocrinol Metab. 2008 Dec;93(12):4759-66. (PMID: 18826998); Pediatr Diabetes. 2008 Jun;9(3 Pt 1):197-201. (PMID: 18547233); Cell. 1997 May 16;89(4):587-96. (PMID: 9160750); Cell Res. 2006 Jan;16(1):3-10. (PMID: 16467870); Clin Immunol. 2018 Mar;188:103-112. (PMID: 29330114); N Engl J Med. 2005 Jun 23;352(25):2598-608. (PMID: 15972866); Lancet. 2011 Aug 6;378(9790):487-97. (PMID: 21719095); F1000Res. 2014 Feb 05;3:37. (PMID: 25580220); Diabetes Care. 2020 Jan;43(1):5-12. (PMID: 31753960); Diabetologia. 2010 Apr;53(4):614-23. (PMID: 20225393); Diabetes. 2013 Jul;62(7):2500-8. (PMID: 23454692); Blood. 2011 Sep 8;118(10):2809-20. (PMID: 21719603); Diabetes Care. 2009 Aug;32(8):1384-90. (PMID: 19435955); Pediatr Diabetes. 2006 Apr;7( ):101-7. (PMID: 16629716); Diabetologia. 2014 Feb;57(2):366-72. (PMID: 24264051); Diabetes. 2005 Dec;54 Suppl 2:S32-9. (PMID: 16306337); J Exp Med. 2004 Sep 20;200(6):725-35. (PMID: 15381728); Science. 2005 Jan 21;307(5708):430-3. (PMID: 15662016); Expert Opin Biol Ther. 2002 Apr;2(4):431-41. (PMID: 11955280); J Clin Invest. 2015 Aug 3;125(8):3285-96. (PMID: 26193635); Science. 2002 Jan 11;295(5553):338-42. (PMID: 11786644); Br J Dermatol. 2003 Apr;148(4):784-8. (PMID: 12752139); Diabetologia. 2018 Nov;61(11):2356-2370. (PMID: 30167736); Annu Rev Immunol. 2004;22:745-63. (PMID: 15032595); Nat Immunol. 2005 Nov;6(11):1123-32. (PMID: 16200070); Immunity. 2009 Jun 19;30(6):899-911. (PMID: 19464196). Linking ISSN: 23793708. Subset: MEDLINE; Grant Information: R01 CA185349 United States CA NCI NIH HHS; UM1 AI109565 United States AI NIAID NIH HHS Date of Electronic Publication: 2021 Jan 25. ; Original Imprints: Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- <br />