9126705

pubmed:Citation

3

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.

eng

IM

MEDLINE

1043-4666

Print

NLM

166-77

pubmed-meshheading:9126705-Animals, pubmed-meshheading:9126705-Antibodies, Monoclonal, pubmed-meshheading:9126705-Antigen-Presenting Cells, pubmed-meshheading:9126705-Antigens, CD, pubmed-meshheading:9126705-Antigens, CD28, pubmed-meshheading:9126705-Antigens, CD40, pubmed-meshheading:9126705-Cell Communication, pubmed-meshheading:9126705-Cell Cycle Proteins, pubmed-meshheading:9126705-Cell Line, pubmed-meshheading:9126705-Clone Cells, pubmed-meshheading:9126705-Female, pubmed-meshheading:9126705-GTP-Binding Proteins, pubmed-meshheading:9126705-Interleukin-4, pubmed-meshheading:9126705-Mice, pubmed-meshheading:9126705-Mice, Inbred BALB C, pubmed-meshheading:9126705-Mice, Inbred CBA, pubmed-meshheading:9126705-Phosphoprotein Phosphatases, pubmed-meshheading:9126705-Polymerase Chain Reaction, pubmed-meshheading:9126705-RNA, Messenger, pubmed-meshheading:9126705-Receptors, Interleukin, pubmed-meshheading:9126705-Receptors, Interleukin-4, pubmed-meshheading:9126705-Solubility, pubmed-meshheading:9126705-Th1 Cells, pubmed-meshheading:9126705-Th2 Cells, pubmed-meshheading:9126705-ras-GRF1

The production of soluble interleukin 4 receptors is preferentially regulated by the murine Th2 cell subset.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't