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

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.

SUBMITTER: Schwedhelm K 

PROVIDER: S-EPMC5564451 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Schwedhelm Katharine K   Thorpe Jerill J   Murray Sara A SA   Gavin Marc M   Speake Cate C   Greenbaum Carla C   Cerosaletti Karen K   Buckner Jane J   Long S Alice SA  

Clinical immunology (Orlando, Fla.) 20170620

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 restin  ...[more]

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