Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway

Immunity. 2006 Jun;24(6):787-799. doi: 10.1016/j.immuni.2006.03.024.


Here, we describe a previously unrecognized pathway for activation of antigen-specific adaptive immune responses that was independent of Toll-Interleukin 1 Receptor signaling and directed toward detection of antigens expressed by apoptotic cells. This pathway is represented within Flt-3 Ligand-derived dendritic cells (DCs) that represent immature lymphoid DCs, but not within GM-CSF-treated bone marrow-derived dendritic cells. Exposure of these DCs to apoptotic cells resulted in production of type I interferon and favored the development of cytotoxic T cell responses. The N-Ethyl-N-Nitrosourea-induced germline mutation 3d (Unc3b1(3d/3d)) abolished both MHC class I and II responses elicited by this pathway, whereas a null allele of Cd36 selectively abolished class II responses. We propose that this mode of adaptive immune activation evolved to permit the sensitive detection of intracellular microbial infections, particularly viral infections, which frequently induce apoptotic cell death, but may also be important in transplantation, autoimmunity, and vaccine development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic*
  • Dendritic Cells / immunology
  • Infections / immunology
  • Interferon Type I / metabolism
  • Lymphocyte Activation*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Receptors, Interleukin-1 / physiology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Toll-Like Receptors / physiology


  • CD36 Antigens
  • Interferon Type I
  • Membrane Proteins
  • Membrane Transport Proteins
  • Receptors, Interleukin-1
  • Toll-Like Receptors
  • UNC93B1 protein, mouse
  • flt3 ligand protein