Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1 diabetes

J Immunol. 2010 Oct 1;185(7):3814-8. doi: 10.4049/jimmunol.1001860. Epub 2010 Sep 1.

Abstract

CD4(+)FOXP3(+) regulatory T cells are essential for immune tolerance, and murine studies suggest that their dysfunction can lead to type 1 diabetes (T1D). Human studies assessing regulatory T cell dysfunction in T1D have relied on analysis of FOXP3-expressing cells. Recently, distinct subsets of CD4(+)FOXP3(+) T cells with differing function were identified. Notably, CD45RA(-)CD25(int)FOXP3(low) T cells lack suppressive function and secrete the proinflammatory cytokine IL-17. Therefore, we evaluated whether the relative fractions of CD4(+)FOXP3(+) subsets are altered in new-onset T1D subjects. We report that children with new-onset T1D have an increased proportion of CD45RA(-)CD25(int)FOXP3(low) cells that are not suppressive and secrete significantly more IL-17 than other FOXP3(+) subsets. Moreover, these T1D subjects had a higher proportion of both CD4(+) and CD8(+) T cells that secrete IL-17. The bias toward IL-17-secreting T cells in T1D suggests a role for this proinflammatory cytokine in the pathogenesis of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Separation
  • Child
  • Diabetes Mellitus, Type 1 / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology
  • Humans
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Leukocyte Common Antigens / biosynthesis
  • Leukocyte Common Antigens / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Leukocyte Common Antigens