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A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell

Author

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  • John Paul Ridge

    (Ghost lab, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, NIAID/NIH Building 4 Room 111)

  • Francesca Di Rosa

    (Ghost lab, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, NIAID/NIH Building 4 Room 111
    Unit di Immunologia, I Clinica Medica, Policlinico Umberto I)

  • Polly Matzinger

    (Ghost lab, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, NIAID/NIH Building 4 Room 111)

Abstract

To generate an immune response, antigen-specific T-helper and T-killer cells must find each other and, because they cannot detect each other's presence, they are brought together by an antigen-loaded dendritic cell that displays antigens to both1,2,3. This three-cell interaction, however, seems nearly impossible because all three cell types are rare and migratory. Here we provide a potential solution to this conundrum. We found that the three cells need not meet simultaneously but that the helper cell can first engage and ‘condition’ the dendritic cell, which then becomes empowered to stimulate a killer cell. The first step (help) can be bypassed by modulation of the surface molecule CD40, or by viral infection of dendritic cells. These results may explain the longstanding paradoxical observation that responses to some viruses are helper-independent, and they evoke the possibility that dendritic cells may take on different functions in response to different conditioning signals.

Suggested Citation

  • John Paul Ridge & Francesca Di Rosa & Polly Matzinger, 1998. "A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell," Nature, Nature, vol. 393(6684), pages 474-478, June.
  • Handle: RePEc:nat:nature:v:393:y:1998:i:6684:d:10.1038_30989
    DOI: 10.1038/30989
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    Cited by:

    1. Diego Calzada-Fraile & Salvador Iborra & Marta Ramírez-Huesca & Inmaculada Jorge & Enrico Dotta & Elena Hernández-García & Noa Martín-Cófreces & Estanislao Nistal-Villán & Esteban Veiga & Jesús Vázque, 2023. "Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Kieran English & Rain Kwan & Lauren E. Holz & Claire McGuffog & Jelte M. M. Krol & Daryan Kempe & Tsuneyasu Kaisho & William R. Heath & Leszek Lisowski & Maté Biro & Geoffrey W. McCaughan & David G. B, 2024. "A hepatic network of dendritic cells mediates CD4 T cell help outside lymphoid organs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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