CD43 regulates Th2 differentiation and inflammation

J Immunol. 2008 Jun 1;180(11):7385-93. doi: 10.4049/jimmunol.180.11.7385.

Abstract

CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43(-/-) T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43(-/-) T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43(-/-) T cells preferentially differentiated into Th2 cells in vitro, and CD43(-/-) T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43(-/-) mice exhibited increased inflammation in two separate models of Th2-mediated allergic airway disease. In contrast, in Th1-mediated diabetes, nonobese diabetic CD43(-/-) mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to MOG(35-55) was also normal in the CD43(-/-) mice. Nonetheless, the CD43(-/-) mice produced more IL-5 when restimulated with MOG(35-55) in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43(-/-) T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Th1-mediated autoimmune responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmunity / immunology
  • Calcium / metabolism
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • GATA3 Transcription Factor / metabolism
  • Immunoglobulin E / blood
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / immunology
  • Interleukin-5 / metabolism
  • Leukosialin / immunology
  • Leukosialin / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell / immunology
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukin-5
  • Leukosialin
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Immunoglobulin E
  • Calcium