PLoS One. 2010 Sep 23;5(9):e12868.

Inhibition of effector function but not T cell activation and increase in FoxP3 expression in T cells differentiated in the presence of PP14.

Ochanuna Z, Geiger-Maor A, Dembinsky-Vaknin A, Karussis D, Tykocinski ML, Rachmilewitz J.

Source

Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract

BACKGROUND:

T-helper polarization of naïve T cells is determined by a complex mechanism that involves many factors, eventually leading to activation of Th1, Th2, or Th17 responses or alternatively the generation of regulatory T cells. Placental Protein 14 (PP14) is a 28 kDa glycoprotein highly secreted in early pregnancy that is able to desensitize T cell receptor (TCR) signaling and modulate T cell activation.

METHODOLOGY/PRINCIPAL FINDINGS:

Prolonged antigen-specific stimulation of T cells in the presence of PP14 resulted in an impaired secretion of IFN-γ, IL-5 and IL-17 upon restimulation, although the cells proliferated and expressed activation markers. Furthermore, the generation of regulatory CD4(+)CD25(high)Foxp3(+) T cells was induced in the presence of PP14, in both antigen-specific as well as polyclonal stimulation. In accordance with previous reports, we found that the induction of FoxP3 expression by PP14 is accompanied by down regulation of the PI3K-mTOR signaling pathway.

CONCLUSIONS/SIGNIFICANCE:

These data suggest that PP14 arrests T cells in a unique activated state that is not accompanied with the acquisition of effector function, together with promoting the generation of regulatory T cells. Taken together, our results may elucidate the role of PP14 in supporting immune tolerance in pregnancy by reducing T cell effector functions along with augmenting Treg differentiation.