Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking.
The orphan receptor T1/ST2, a member of the IL-1R family, is preferentially expressed on the surface of murine Th2 cells. In this study, we analyzed the kinetics and function of T1/ST2 expression on Th2 cells in vitro. Whereas naive CD4(+) cells did not express T1/ST2, most CD4(+) cells became T1/ST2(+) upon repeated antigenic stimulation under Th2-polarizing conditions. Flow cytometric analyses revealed that the kinetics of T1/ST2 expression on Th2 cells was delayed compared with the kinetics of type 2 cytokine production. Exogenous IL-6, IL-5, IL-1, and TNF-alpha enhanced the expression of T1/ST2 on Th2 cells, and IL-6 was by far most effective in this regard. However, the expression of T1/ST2 did not depend on the presence of IL-6 and was also detected in IL-6-deficient mice. Most important, cross-linking of T1/ST2 provided a costimulatory signal for Th2 but not Th1 cells and directly induced proliferation and type 2 cytokine production. Thus, T1/ST2 is not only a Th2 cell marker but also plays an important role in the activation of Th2 cells.
Meisel
C
C
Deutsches Rheumaforschungszentrum, Berlin, Germany.
Bonhagen
K
K
Löhning
M
M
Coyle
A J
AJ
Gutierrez-Ramos
J C
JC
Radbruch
A
A
Kamradt
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016853:Muromonab-CD3 / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D018123:Receptors, Interleukin; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015848:Interleukin-5; D015850:Interleukin-6; D008565:Membrane Proteins; D016853:Muromonab-CD3; D011506:Proteins; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4