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

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

Author information

1
Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
2
Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA.
3
Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, WA, USA.
4
Translational Research Program, Benaroya Research Institute, Seattle, WA, USA. Electronic address: along@benaroyaresearch.org.

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

PMID:
28645874
PMCID:
PMC5564451
DOI:
10.1016/j.clim.2017.06.004
[Indexed for MEDLINE]
Free PMC Article

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