CD47 expression on T cell is a self-control negative regulator of type 1 immune response

J Immunol. 2008 Jun 15;180(12):8073-82. doi: 10.4049/jimmunol.180.12.8073.

Abstract

The cytokine milieu and dendritic cells (DCs) direct Th1 development. Yet, the control of Th1 polarization by T cell surface molecules remains ill-defined. We here report that CD47 expression on T cells serves as a self-control mechanism to negatively regulate type 1 cellular and humoral immune responses in vivo. Th2-prone BALB/c mice that lack CD47 (CD47(-/-)) displayed a Th1-biased Ab profile at steady state and after immunization with soluble Ag. CD47(-/-) mice mounted a T cell-mediated exacerbated and sustained contact hypersensitivity (CHS) response. After their adoptive transfer to naive CD47-deficient hosts 1 day before immunization with soluble Ag, CD47(-/-) as compared with CD47(+/+)CD4(+) transgenic (Tg) T cells promoted the deviation of Ag-specific T cell responses toward Th1 that were characterized by a high IFN-gamma:IL-4 cytokine ratio. Although selective CD47 deficiency on DCs led to increased IL-12p70 production, CD47(-/-)Tg T cells produced more IFN-gamma and displayed higher T-bet expression than CD47(+/+) Tg T cells in response to OVA-loaded CD47(-/-) DCs. CD47 as part of the host environment has no major contribution to the Th1 polarization responses. We thus identify the CD47 molecule as a T cell-negative regulator of type 1 responses that may limit unwanted collateral damage to maximize protection and minimize host injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD47 Antigen / biosynthesis*
  • CD47 Antigen / genetics*
  • CD47 Antigen / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / pathology
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Gene Expression Regulation / immunology*
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*

Substances

  • CD47 Antigen
  • Cd47 protein, mouse
  • Inflammation Mediators