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A Novel Mutation in CD83 Results in the Development of a Unique Population of CD4⁺ T Cells

Celltech Research & Development, Bothell, WA 98021

Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4⁺ T cells and for their function postactivation. CD11c⁺ dendritic cells develop and function normally in mice with a mutated CD83 gene but CD4⁺ T cell development is substantially reduced. Additionally, we now show that those CD4⁺ cells that develop in a CD83 mutant animal fail to respond normally following allogeneic stimulation. This is at least in part due to an altered cytokine expression pattern characterized by an increased production of IL-4 and IL-10 and diminished IL-2 production. Thus, in addition to its role in selection of CD4⁺ T cells, absence of CD83 results in the generation of cells with an altered activation and cytokine profile.

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