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.
Goetzl
E J
EJ
Department of Medicine, University of California, San Francisco, CA 94143, USA. egoetzel@itsa.ucsf.edu
Kong
Y
Y
Voice
J K
JK
D000276:Adjuvants, Immunologic / Q000502:physiology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008246:Lysophospholipids / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000502:physiology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; C060506:sphingosine 1-phosphate; D013110:Sphingosine