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RESEARCH COMMUNICATION |
over IL-4 responses
a Department of Immunology, The University of Manitoba, Winnipeg, Canada
b Department of Pediatrics and Child Health, The University of Manitoba, Winnipeg, Canada
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 (IFN-) 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-:IL-4 ratios. Selective enhancement of IFN- 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- 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.—Gangur, V., Simons, F. E. R., HayGlass, K. T. Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN- over IL-4 responses. FASEB J. 12, 705–713 (1998)
Key Words: environmental antigens • Th1/Th2 subsets • chemokine • TNF • interleukin • interferon
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