Immunological effects of transgenic constitutive expression of the type 1 sphingosine 1-phosphate receptor by mouse lymphocytes.
The type 1 sphingosine 1-phosphate (S1P) G protein-coupled receptor (S1P1) normally transduces S1P effects on lymph node (LN) egress and tissue migration of naive lymphocytes. We now show that persistent expression of S1P1 by lymphocytes of S1P1-transgenic (Tg) mice suppresses delayed-type hypersensitivity and results in production of significantly more IgE Ab and less IgG2 Ab than in wild-type (wt) mice. wt host LN homing of 51Cr-labeled T cells from S1P1-Tg mice was only 30-40% of that for wt T cells. Adoptive-transfer of dye-labeled activated T cells from S1P1-Tg mice into wt mice resulted in 2.2-fold more in blood and 60% less in LNs than for activated wt T cells after 1 day. Proliferative responses of stimulated T cells from S1P1-Tg mice were only 10-34% of those for wt T cells. Disordered cellular and humoral immunity of S1P1-Tg mice thus may be attributable to both altered T cell traffic and depressed T cell functions, suggesting that S1P1-specific agonists may represent a novel therapeutic approach to autoimmunity and transplant rejection.
Gräler
Markus H
MH
Institute for Immunology, Hannover Medical School, Hannover, Germany.
Huang
Mei-Chuan
MC
Watson
Susan
S
Goetzl
Edward J
EJ
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018801:CD2 Antigens / Q000235:genetics; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D018801:CD2 Antigens; D006131:Growth Inhibitors; D049349:Receptors, Lysosphingolipid