THE PRODUCTION OF SOLUBLE INTERLEUKIN 4 RECEPTORS IS PREFERENTIALLY REGULATED BY THE MURINE Th 2CELL SUBSET

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 1997, Vol.9 (3), p.166-177
• Main Authors: Fernandez-Botran, Rafael, Chilton, Paula M., Ma, Yuhe, Windsor, Jana L., Street, Nancy E.
• Format: Article
• Language: English
• Subjects: CD4 +T cell subsets; IL-4; immunoregulation; soluble interleukin 4 receptor
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1996.0151

In order to understand how the endogenous production of soluble IL-4 receptors (sIL-4r) is regulated, the authors tested prototypic clones of Th 1and Th 2murine 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 Th 2clones upregulated sIL-4r expression following antigenic stimulation. Inhibition of endogenous IL-4 with a neutralizing anti-IL-4 mAb had only a minor (≈20%) inhibitory effect on sIL-4r production by the Th 2cells, and addition of rIL-4 to Th 1cells 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 Th 2clones to upregulate sIL-4r expression can be relatively independent of IL-4. Indeed, the production of sIL-4r by Th 2cells 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 Th 1and Th 2cells, with the relative levels of expression being moderately higher in the Th 2clones. Moreover, the expression of sIL-4r-specific transcripts appeared to increase to a greater extent than those of mIL-4r after activation of Th 2cells 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 Th 2-type responses and indicate that even though the production of IL-4 and sIL-4r is mediated by the same cells (i.e. Th 2cells), 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.