Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state

Clin Immunol. 2017 Aug;181:67-74. doi: 10.1016/j.clim.2017.06.004. Epub 2017 Jun 20.

Abstract

The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. Comparing basal IL-2 responses in resting versus activated cells, memory Teff displayed lower, but more sustained, responses to IL-2 overtime. These results suggest that T1D-associated defects in the Teff compartment are due to intrinsic factors related to activation. Evaluation of both Teff and Treg IL-2R signaling defects in T1D subjects may inform selection of therapies.

Keywords: Activation; CD4 T cell; IL-2; Signaling; Type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-2 / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / immunology*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • Young Adult

Substances

  • IL2 protein, human
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2