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

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.

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Figure 1: Two models of the delivery of help to CD8+ killers.
Figure 2: Four ways to help a killer.
Figure 3: Summary of 117 tests showing five ways to help a killer.
Figure 4: B.71 and B7.2 are involved in stimulation of killer cells by conditioned dendritic cells.
Figure 5: Virgin killers can be primed in vivo by CD40-modulated dendritic cells.

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Acknowledgements

We thank C. Anderson for skin grafting; O. Lantz for the use of his unpublished TCR trangenic mouse; H. Arnheiter, A. Bendelac, L. D'Adamio, R. Germain, R. Schwartz and members of the Ghost lab (O. Alpan, C. Anderson, S. Celli, A. Frank, S. Galluci, T. Kamala, R. Weiss) for reading the manuscript and for useful suggestions; and D. Faherty, K. Hathcock and P. Linsley for blocking reagents.

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Correspondence to John Paul Ridge.

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Ridge, J., Di Rosa, F. & Matzinger, P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393, 474–478 (1998). https://doi.org/10.1038/30989

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