Th17 Augmentation in OTII TCR Plus T Cell-Selective Type 1 Sphingosine 1-Phosphate Receptor Double Transgenic Mice

• Published in: Journal of Immunology Vol. 178; no. 11; pp. 6806 - 6813
• Main Authors: Huang, Mei-Chuan, Watson, Susan R, Liao, Jia-Jun, Goetzl, Edward J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.2007
• Subjects: Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Migration Inhibition; Down-Regulation - immunology; Humans; Immunoglobulin G - biosynthesis; Interleukin-17 - biosynthesis; Interleukin-17 - genetics; Interleukin-17 - metabolism; Intracellular Fluid - immunology; Intracellular Fluid - metabolism; Lysophospholipids - biosynthesis; Lysophospholipids - genetics; Lysophospholipids - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Lysosphingolipid - genetics; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sphingosine - analogs & derivatives; Sphingosine - biosynthesis; Sphingosine - genetics; Sphingosine - physiology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.11.6806

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.