An immune cell-selective interleukin 4 agonist.

A B Shanafelt; C P Forte; J J Kasper; L Sanchez-Pescador; M Wetzel; R Gundel; J M Greve

doi:10.1073/pnas.95.16.9454

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An immune cell-selective interleukin 4 agonist.

A B Shanafelt·C P Forte·J J Kasper·L Sanchez-Pescador·M Wetzel·R Gundel·J M Greve

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Abstract

Interleukin 4 (IL-4) is a pleiotropic cytokine. Of the cell types responsive to IL-4, T cells express one IL-4 receptor (IL-4R) type, IL-4Ralpha/IL-2Rgamma (class I IL-4R), whereas endothelial cells express another type, IL-4Ralpha/IL-13Ralpha (class II IL-4R). It was hypothesized that IL-4 variants could be generated that would be selective for cell types expressing the different IL-4Rs. A series of IL-4 muteins were generated that were substituted in the region of IL-4 implicated in interactions with IL-2Rgamma. These muteins were evaluated in T cell and endothelial cell assays. One of these muteins, containing the mutation Arg-121 to Glu (IL-4/R121E), exhibited complete biological selectivity for T cells, B cells, and monocytes, but showed no activity on endothelial cells. Receptor binding studies indicated that IL-4/R121E retained physical interaction with IL-2Rgamma but not IL-13Ralpha; consistent with this observation, IL-4/R121E was an antagonist of IL-4-induced activity on endothelial cells. IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases.

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B-Lymphocytes Binding, Competitive Cells, Cultured Endothelium, Vascular Humans Interleukin-4 Receptors, Interleukin-4 T-Lymphocytes Journal Article

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A B Shanafelt, C P Forte, J J Kasper, L Sanchez-Pescador, M Wetzel, R Gundel, J M Greve. 1998-08-04. An immune cell-selective interleukin 4 agonist.. https://doi.org/10.1073/pnas.95.16.9454

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