Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-T_FH cells.

ABSTRACT: Sustained T cell receptor (TCR) stimulation is required for maintaining germinal center T follicular helper (GC-T_FH) cells. Paradoxically, TCR activation induces interleukin-2 receptor (IL-2R) expression and IL-2 production, thereby initiating a feedback loop of IL-2 signaling that normally inhibits T_FH cells. It is unclear how GC-T_FH cells can receive prolonged TCR signaling without succumbing to the detrimental effects of IL-2. Using an influenza infection model, we show here that GC-T_FH cells secreted large amounts of IL-2 but responded poorly to it. To maintain their IL-2 hyporesponsiveness, GC-T_FH cells required intrinsic IL-6 signaling. Mechanistically, we found that IL-6 inhibited up-regulation of IL-2Rβ (CD122) by preventing as

SUBMITTER: Papillion A 

PROVIDER: S-EPMC6820141 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature