Th17 augmentation in OTII TCR plus T cell-selective type 1 sphingosine 1-phosphate receptor double transgenic mice.
Sphingosine 1-phosphate (S1P) in blood and lymph controls lymphoid traffic and tissue migration of T cells through signals from the type 1 S1PR (S1P(1)), but less is known of effects of the S1P-S1P(1) axis on nonmigration functions of T cells. CD4 T cells from a double transgenic (DTG) mouse express OTII TCRs specific for OVA peptide 323-339 (OVA) and a high level of transgenic S1P(1), resistant to suppression by T cell activation. OVA-activated DTG CD4 T cells respond as expected to S1P by chemotactic migration and reduction in secretion of IFN-gamma. In addition, DTG CD4 T cells stimulated by OVA secrete a mean of 2.5-fold more IL-17 than those from OTII single transgenic mice with concomitantly higher levels of mRNA encoding IL-17 by real-time PCR and of CD4 T cells with intracellular IL-17 detected by ELISPOT assays. OVA challenge of s.c. air pockets elicited influx of more OTII TCR-positive T cells producing a higher level of IL-17 in DTG mice than OTII control mice. Augmentation of the number and activity of Th17 cells by the S1P-S1P(1) axis may thus enhance host defense against microbes and in other settings increase host susceptibility to autoimmune diseases.
Huang
Mei-Chuan
MC
Department of Medicine and Department of Microbiology-Immunology, University of California, San Francisco, CA 94143, USA.
Watson
Susan R
SR
Liao
Jia-Jun
JJ
Goetzl
Edward J
EJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002464:Cell Migration Inhibition; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D049349:Receptors, Lysosphingolipid / Q000235:genetics*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D007074:Immunoglobulin G; D020381:Interleukin-17; D008246:Lysophospholipids; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D010047:Ovalbumin; D013110:Sphingosine