Interaction between Phosphatidylserine and the Phosphatidylserine Receptor Inhibits Immune Responses In Vivo

• Published in: The Journal of immunology (1950) 2005-02, Vol.174 (3), p.1393-1404
• Main Authors: Hoffmann, Peter R, Kench, Jennifer A, Vondracek, Andrea, Kruk, Ellen, Daleke, David L, Jordan, Michael, Marrack, Philippa, Henson, Peter M, Fadok, Valerie A
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - immunology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Movement - drug effects; Cell Movement - immunology; Cells, Cultured; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Epitopes, T-Lymphocyte - immunology; Germinal Center - drug effects; Germinal Center - immunology; Germinal Center - metabolism; Hybridomas; Immune Sera - administration & dosage; Immune Sera - blood; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - metabolism; Injections, Subcutaneous; Lipopolysaccharides - pharmacology; Liposomes; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymph Nodes - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Oligodeoxyribonucleotides - pharmacology; Ovalbumin - administration & dosage; Ovalbumin - immunology; Phosphatidylserines - administration & dosage; Phosphatidylserines - metabolism; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Spleen - drug effects; Spleen - immunology; Spleen - metabolism; Stereoisomerism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.3.1393

Phosphatidylserine (PS) on apoptotic cells promotes their uptake and induces anti-inflammatory responses in phagocytes, including TGF-beta release. Little is known regarding the effects of PS on adaptive immune responses. We therefore investigated the effects of PS-containing liposomes on immune responses in mice in vivo. PS liposomes specifically inhibited responses to Ags as determined by decreased draining lymph node tissue mass, with reduced numbers of total leukocytes and Ag-specific CD4(+) T cells. There was also a decrease in formation and size of germinal centers in spleen and lymph nodes, accompanied by decreased levels of Ag-specific IgG in blood. Many of these effects were mimicked by an agonistic Ab-specific for the PS receptor. TGF-beta appears to play a critical role in this inhibition, as the inhibitory effects of PS were reversed by in vivo administration of anti-TGF-beta Ab. PS-containing liposomes did not appear to directly inhibit dendritic cell maturation in vitro in response to a variety of stimuli, nor did it prevent their migration to regional lymph nodes in vivo, suggesting that the inhibitory effects may have resulted from complicated interactions between tissue cells and dendritic cells, subsequently inhibiting their ability to productively activate T lymphocytes.