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Forced Expression of the Fc Receptor -Chain Renders Human T Cells Hyperresponsive to TCR/CD3 Stimulation ¹

Madhusoodana P. Nambiar^*,, Carolyn U. Fisher^*, Anil Kumar^*, Christos G. Tsokos^*, Vishal G. Warke^* and George C. Tsokos^2,*,

^* Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910; and Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

High level expression of FcRI chain replaces the deficient TCR -chain and contributes to altered TCR/CD3-mediated signaling abnormalities in T cells of patients with systemic lupus erythematosus. Increased responsiveness to Ag has been considered to lead to autoimmunity. To test this concept, we studied early signaling events and IL-2 production in fresh cells transfected with a eukaryotic expression vector encoding the FcRI gene. We found that the overexpressed FcRI chain colocalizes with the CD3 chain on the surface membrane of T cells and that cross-linking of the new TCR/CD3 complex leads to a dramatic increase of intracytoplasmic calcium concentration, protein tyrosine phosphorylation, and IL-2 production. We observed that overexpression of FcRI is associated with increased phosphorylation of Syk kinase, while the endogenous TCR -chain is down-regulated. We propose that altered composition of the CD3 complex leads to increased T cell responsiveness to TCR/CD3 stimulation and sets the biochemical grounds for the development of autoimmunity.

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The JI 2003 170: 2795-2796. [Full Text]  

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