T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses.
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.
Townsend
M J
MJ
Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.
Fallon
P G
PG
Matthews
D J
DJ
Jolin
H E
HE
McKenzie
A N
AN
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D015769:Granuloma, Respiratory Tract / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007275:Injections, Intravenous; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010063:Ovum / Q000276:immunology; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012550:Schistosoma mansoni / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology
D000947:Antigens, Helminth; D016207:Cytokines; C486189:Il1rl1 protein, mouse; D007132:Immunoglobulin Isotypes; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D011506:Proteins; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1