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Cutting Edge: Regulation of T Cell Trafficking and Primary Immune Responses by Sphingosine 1-Phosphate Receptor 1

Hongbo Chi^* and Richard A. Flavell^1,*,

^* Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute, New Haven, CT 06520

Signaling by sphingosine 1-phosphate (S1P) through its receptor S1P₁ has recently been shown to promote thymocyte egress. In the periphery, S1P₁ is expressed on naive T cells but lost upon T cell activation. To determine the significance of S1P₁ down-regulation and function of S1P₁ in peripheral T cells, we developed transgenic mice that constitutively express S1P₁ in T cells. Mature T cells from these mice exhibited enhanced chemotactic response toward S1P, and preferentially distributed to the blood rather than secondary lymphoid organs. S1P₁-transgenic mice showed significant delay in the onset of experimental autoimmune encephalomyelitis, and had defective contact hypersensitivity reaction and local Ag-induced responses. These impairments were associated with reduced numbers of Ag-activated T cells in the draining lymph nodes. Our studies demonstrate that S1P₁ signaling affects systemic trafficking of peripheral T cells and immune responses and highlight that levels of S1P₁ expression represent an important mechanism of immune regulation.

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