Differential Regulation of Th1/Th2 Cytokine Responses by Placental Protein 14

• Published in: The Journal of immunology (1950) Vol. 173; no. 9; pp. 5524 - 5530
• Main Authors: Mishan-Eisenberg, Galit, Borovsky, Zipora, Weber, Matthew C, Gazit, Roi, Tykocinski, Mark L, Rachmilewitz, Jacob
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.2004
• Subjects: Amniotic Fluid - immunology; Amniotic Fluid - physiology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells, Cultured; Cytokines - biosynthesis; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - biosynthesis; Down-Regulation - genetics; Down-Regulation - immunology; Enterotoxins - pharmacology; GATA3 Transcription Factor; Glycodelin; Glycoproteins - deficiency; Glycoproteins - genetics; Glycoproteins - physiology; Humans; Pregnancy Proteins - deficiency; Pregnancy Proteins - genetics; Pregnancy Proteins - physiology; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; Trans-Activators - antagonists & inhibitors; Trans-Activators - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.9.5524

The potency of TCR signaling during primary CD4+ T cell activation influences initial cytokine expression patterns and subsequent polarization toward either Th1 or Th2 subsets. In this study, we demonstrate that the T cell inhibitor placental protein 14 (PP14; glycodelin) preferentially inhibits Th1 cytokine responses and chemokine expression when present during ex vivo priming of CD4+ T cells. PP14 synergizes with exogenously added IL-4 in skewing T cell responses. Significantly, PP14 impairs the down-regulation of GATA-3 transcriptional regulator expression that normally accompanies T cell activation, which is a prerequisite for Th1 development. Taken together, these data document for the first time the ability of PP14 to skew Th responses.