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

J Exp Med. 2000 Mar 20;191(6):1069-76. doi: 10.1084/jem.191.6.1069.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / administration & dosage
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Crosses, Genetic
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Granuloma, Respiratory Tract / genetics
  • Granuloma, Respiratory Tract / immunology
  • Granuloma, Respiratory Tract / parasitology
  • Immunoglobulin Isotypes / biosynthesis
  • Injections, Intravenous
  • Interleukin-1 Receptor-Like 1 Protein
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovum / immunology
  • Proteins / genetics*
  • Proteins / physiology
  • Receptors, Interleukin
  • Receptors, Interleukin-1 / physiology
  • Schistosoma mansoni / immunology
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / parasitology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*
  • Th2 Cells / parasitology

Substances

  • Antigens, Helminth
  • Cytokines
  • Il1rl1 protein, mouse
  • Immunoglobulin Isotypes
  • Interleukin-1 Receptor-Like 1 Protein
  • Membrane Proteins
  • Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-1