Placental protein 14 functions as a direct T-cell inhibitor

Human placental protein 14 (PP14, also referred to as glycodelin and proges terone-associated endometrial protein) inhibits phytohemagglutinin (PHA)-st imulated T-cell proliferation and monokine secretion within PBMC population s. However, the mechanisms underlying these and other PP14 immunoinhibitory activities remain unclear. In the present study, we asked whether PP14's T -cell inhibitory effect is a direct one or, alternatively, an indirect cons equence of accessory cell (AC) perturbation. Using either immunopurified PP 14 or first-trimester amniotic fluid (AF) as a rich source of PP14, we docu mented inhibition of the proliferation of highly purified peripheral blood T-cells when stimulated with anti-CD3 mAbs or PHA in the presence of parafo rmaldehyde-fixed AC. Significantly, PP14 inhibited T cell proliferation and IL-2 secretion induced by immobilized anti-CD3 and anti-CD28 mAbs in the a bsence of AC. PP14 depletion (via immunoprecipitation) abrogated AF's T-cel l inhibitory activity, indicating that the PP14 within the amniotic fluid i s required for this immunoregulatory effect. These findings establish that PP14 can inhibit T-cell proliferation in the absence of AC and thus add PP1 4 to the relatively restricted set of immunoinhibitory proteins that are kn own to target T cells directly. Additional data demonstrate that PP14's inh ibitory effect can be overridden by stimuli which circumvent early events d uring T-cell receptor (TCR) activation, namely, protein kinase C activators in combination with Ca2+ ionophores. These latter results suggest that PP1 4 inhibits early events in the TCR signaling pathway. (C) 1999 Academic Pre ss.