Protein Kinase Cε Regulates Proliferation and Cell Sensitivity to TGF-1β of CD4+ T Lymphocytes: Implications for Hashimoto Thyroiditis

We have studied the functional role of protein kinase Cε (PKCε) in the control of
human CD4(+) T cell proliferation and in their response to TGF-1β. We demonstrate
that PKCε sustains CD4(+) T cell proliferation triggered in vitro by CD3
stimulation. Transient knockdown of PKCε expression decreases IL-2R chain
transcription, and consequently cell surface expression levels of CD25. PKCε
silencing in CD4 T cells potentiates the inhibitory effects of TGF-1β, whereas in
contrast, the forced expression of PKCε virtually abrogates the inhibitory
effects of TGF-1β. Being that PKCε is therefore implicated in the response of CD4
T cells to both CD3-mediated proliferative stimuli and TGF-1β antiproliferative
signals, we studied it in Hashimoto thyroiditis (HT), a pathology characterized
by abnormal lymphocyte proliferation and activation. When we analyzed CD4 T cells
from HT patients, we found a significant increase of PKCε expression, accounting
for their enhanced survival, proliferation, and decreased sensitivity to TGF-1β.
The increased expression of PKCε in CD4(+) T cells of HT patients, which is
described for the first time, to our knowledge, in this article, viewed in the
perspective of the physiological role of PKCε in normal Th lymphocytes, adds
knowledge to the molecular pathophysiology of HT and creates potentially new
pharmacological targets for the therapy of this disease.