T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses

被引:426
作者
Townsend, MJ
Fallon, PG
Matthews, DJ
Jolin, HE
McKenzie, ANJ
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
基金
英国惠康基金;
关键词
T1/ST2; T helper type 2 cells; immunoglobulin; pulmonary inflammation; mast cells;
D O I
10.1084/jem.191.6.1069
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have generated mice with a deficiency in T1/ST2 expression to clarify the roles of T1/ST2 in T helper cell type 2 (Th2) responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of T1/ST2-deficient mice with those generated by wild-type mice. Using a primary pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that granuloma formation, characterized by eosinophil infiltration, is abrogated in T1/ST2-deficient mice. Furthermore, we clearly demonstrate that in the absence of T1/ST2 expression, the levels of Th2 cytokine production are severely impaired after immunization. Thus, in a secondary pulmonary granuloma model, draining lymph node cells from the T1/ST2-deficient animals produced significantly reduced levels of IL-4 and IL-5, despite developing granulomas of a magnitude similar to those of wild-type mice and comparable antigen-specific immunoglobulin isotype production. These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-Like cytokine responses and indicate that effector functions are inhibited in its absence.
引用
收藏
页码:1069 / 1075
页数:7
相关论文
共 35 条
[1]   ALTERNATIVE PROMOTER USAGE OF THE FOS-RESPONSIVE GENE FIT-1 GENERATES MESSENGER-RNA ISOFORMS CODING FOR EITHER SECRETED OR MEMBRANE-BOUND PROTEINS RELATED TO THE IL-1 RECEPTOR [J].
BERGERS, G ;
REIKERSTORFER, A ;
BRASELMANN, S ;
GRANINGER, P ;
BUSSLINGER, M .
EMBO JOURNAL, 1994, 13 (05) :1176-1188
[2]   Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses [J].
Coyle, AJ ;
Lloyd, C ;
Tian, J ;
Nguyen, T ;
Erikkson, C ;
Wang, L ;
Ottoson, P ;
Persson, P ;
Delaney, T ;
Lehar, S ;
Lin, S ;
Poisson, L ;
Meisel, C ;
Kamradt, T ;
Bjerke, T ;
Levinson, D ;
Gutierrez-Ramos, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (07) :895-902
[3]   Interleukin-1 receptor cluster:: Gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q [J].
Dale, M ;
Nicklin, MJH .
GENOMICS, 1999, 57 (01) :177-179
[4]  
Fallon PG, 1998, EUR J IMMUNOL, V28, P1408, DOI 10.1002/(SICI)1521-4141(199804)28:04&lt
[5]  
1408::AID-IMMU1408&gt
[6]  
3.0.CO
[7]  
2-H
[8]   REGULATION OF MURINE INVIVO IGG AND IGE RESPONSES BY A MONOCLONAL ANTI-IL-4 RECEPTOR ANTIBODY [J].
FINKELMAN, FD ;
URBAN, JF ;
BECKMANN, MP ;
SCHOOLEY, KA ;
HOLMES, JM ;
KATONA, IM .
INTERNATIONAL IMMUNOLOGY, 1991, 3 (06) :599-607
[9]   Cytokine regulation of host defense against parasitic gastrointestinal nematodes: Lessons from studies with rodent models [J].
Finkelman, FD ;
SheaDonohue, T ;
Goldhill, J ;
Sullivan, CA ;
Morris, SC ;
Madden, KB ;
Gause, WC ;
Urban, JF .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :505-533
[10]   Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model [J].
Foster, PS ;
Hogan, SP ;
Ramsay, AJ ;
Matthaei, KI ;
Young, IG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :195-201