Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses.
Human interferon-inducible protein 10 ( IP-10) differs from most chemokines in its apparent specificity for activated T lymphocytes. We hypothesized that IP-10 was relevant not only for recruiting T cells to inflammatory sites, but also for regulating cytokine synthesis patterns. We examined the effect of recombinant human IP-10 (rhIP-10) on human interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production by fresh peripheral blood mononuclear cells. We demonstrate for the first time that this CXC chemokine selectively up-regulates human T cell cytokine synthesis, with enhancement selectively targeted to promotion of Th1-like dominance. Superantigen (TSST-1), soluble anti-CD3 mAb, and phytohemagglutinin were used to activate distinct intracellular signaling pathways, thereby inducing quantitatively different IFN-gamma:IL-4 ratios. Selective enhancement of IFN-gamma responses was consistently observed, with median increases of 105-470%. Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4-dependent, chloroquine-sensitive cytokine synthesis. Ag-driven IFN-gamma responses exhibited median 19- to 30-fold increases in the presence of nanomolar concentrations of rhIP-10. IL-4 responses were neither enhanced nor inhibited under any of the conditions tested. These findings suggest a potential role for this T cell-focused chemokine in maintenance of the default Th1-like responses usually seen to environmental Ag and indicate a potential application in the modulation of Ag-driven responses in vivo.[1]References
- Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses. Gangur, V., Simons, F.E., Hayglass, K.T. FASEB J. (1998) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
