Differential regulation of Th1/Th2 cytokine responses by placental protein 14.
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.
Mishan-Eisenberg
Galit
G
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Borovsky
Zipora
Z
Weber
Matthew C
MC
Gazit
Roi
R
Tykocinski
Mark L
ML
Rachmilewitz
Jacob
J
D000653:Amniotic Fluid / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D050990:GATA3 Transcription Factor; D000071816:Glycodelin; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011257:Pregnancy Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D016207:Cytokines; D004268:DNA-Binding Proteins; D004768:Enterotoxins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators; C031818:enterotoxin B, staphylococcal