The production of soluble interleukin 4 receptors is preferentially regulated by the murine Th2 cell subset.
In order to understand how the endogenous production of soluble IL-4 receptors (sIL-4r) is regulated, the authors tested prototypic clones of Th1 and Th2 murine CD4+ T cell subsets for their ability to regulate their expression of sIL-4r. Results showed that although both types of clones produced low levels of sIL-4r under resting conditions, only the Th2 clones upregulated sIL-4r expression following antigenic stimulation. Inhibition of endogenous IL-4 with a neutralizing anti-IL-4 mAb had only a minor (approximately 20%) inhibitory effect on sIL-4r production by the Th2 cells, and addition of rIL-4 to Th1 cells resulted only in a modest two-fold increase in sIL-4r levels, suggesting that IL-4 is not the only factor that regulates sIL-4r production and that the ability of Th2 clones to upregulate sIL-4r expression can be relatively independent of IL-4. Indeed, the production of sIL-4r by Th2 cells was found to be regulated by cell contact and/or IL-1 mediated signals. Transcripts for both sIL-4r and mIL-4r were detected by RT-PCR on both resting and activated Th1 and Th2 cells, with the relative levels of expression being moderately higher in the Th2 clones. Moreover, the expression of sIL-4r-specific transcripts appeared to increase to a greater extent than those of mIL-4r after activation of Th2 cells with APCs, both in the presence and absence of antigen. Taken together, these results predict that increased sIL-4r production in vivo might be preferentially associated with Th2-type responses and indicate that even though the production of IL-4 and sIL-4r is mediated by the same cells (i.e. Th2 cells), the synthesis of sIL-4r can be regulated independently from that of IL-4 through alternative signals such as cell contact and/or IL-1. These properties may allow for changing ratios of sIL-4r to IL-4 and sIL-4r to mIL-4r during different phases of an immune response and are consistent with a regulatory role for sIL-4r on IL-4 activity in vivo.
Fernandez-Botran
R
R
Division of Immunology and Immunopathology, School of Medicine, University of Louisville, KY 40292, USA.
Chilton
P M
PM
Ma
Y
Y
Windsor
J L
JL
Street
N E
NE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002450:Cell Communication; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4; D012995:Solubility; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism*; D020666:ras-GRF1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D019013:CD40 Antigens; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D020666:ras-GRF1; D015847:Interleukin-4; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins