Cutting edge: Differential constitutive expression of functional receptors for lysophosphatidic acid by human blood lymphocytes

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) from platelets and macrophages mediate T cell functions. Endothelial differentiation gene-encoded G protein-coupled receptors (Edg Rs) are specific for S1P (Edg-1, -3, -5, and -8 Rs) and LPA (Edg-2, -4, and -7 Rs), Human T cell tumors express many Edg Rs for both LPA and S1P, In contrast, human blood CD4(+) T cells express predominantly Edg-4, and CD8(+) T cells show only traces of Edg-2 and -5, by quantification of mRNA and Edg R Ags, LPA at 10(-10)-10(-6) M suppressed significantly the secretion of IL-2 from anti-CD3 plus anti-CD28 Ab-challenged CD4(+) T cells, but not CD8(+) T cells. Monoclonal anti-Edg-4 R Ab, like LPA, suppressed stimulated IL-2 secretion from CD4(+) T cells, but not CD8(+) T cells. Constitutive expression of Edg-4 by CD4(+), but not CD8(+), human T cells accounts for differential functional responsiveness of the T cell subsets to LPA.