Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway

Edith Janssen, Koichi Tabeta, Michael J. Barnes, Sophie Rutschmann, Sara McBride, Keith S. Bahjat, Stephen P. Schoenberger, Argyrios N. Theofilopoulos, Bruce Beutler, Kasper Hoebe

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

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 (Unc3b13d/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.

Original languageEnglish (US)
Pages (from-to)787-799
Number of pages13
JournalImmunity
Volume24
Issue number6
DOIs
StatePublished - Jun 2006

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Interleukin-1 Receptors
Dendritic Cells
T-Lymphocytes
Ethylnitrosourea
Antigens
Interferon Type I
Germ-Line Mutation
Adaptive Immunity
Virus Diseases
Granulocyte-Macrophage Colony-Stimulating Factor
Autoimmunity
Cell Death
Vaccines
Transplantation
Bone Marrow
Alleles
Lymphocytes
Infection

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Janssen, E., Tabeta, K., Barnes, M. J., Rutschmann, S., McBride, S., Bahjat, K. S., ... Hoebe, K. (2006). Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway. Immunity, 24(6), 787-799. https://doi.org/10.1016/j.immuni.2006.03.024

Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway. / Janssen, Edith; Tabeta, Koichi; Barnes, Michael J.; Rutschmann, Sophie; McBride, Sara; Bahjat, Keith S.; Schoenberger, Stephen P.; Theofilopoulos, Argyrios N.; Beutler, Bruce; Hoebe, Kasper.

In: Immunity, Vol. 24, No. 6, 06.2006, p. 787-799.

Research output: Contribution to journalArticle

Janssen, E, Tabeta, K, Barnes, MJ, Rutschmann, S, McBride, S, Bahjat, KS, Schoenberger, SP, Theofilopoulos, AN, Beutler, B & Hoebe, K 2006, 'Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway', Immunity, vol. 24, no. 6, pp. 787-799. https://doi.org/10.1016/j.immuni.2006.03.024
Janssen E, Tabeta K, Barnes MJ, Rutschmann S, McBride S, Bahjat KS et al. Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway. Immunity. 2006 Jun;24(6):787-799. https://doi.org/10.1016/j.immuni.2006.03.024
Janssen, Edith ; Tabeta, Koichi ; Barnes, Michael J. ; Rutschmann, Sophie ; McBride, Sara ; Bahjat, Keith S. ; Schoenberger, Stephen P. ; Theofilopoulos, Argyrios N. ; Beutler, Bruce ; Hoebe, Kasper. / Efficient T Cell Activation via a Toll-Interleukin 1 Receptor-Independent Pathway. In: Immunity. 2006 ; Vol. 24, No. 6. pp. 787-799.
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