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Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation

Nature Immunology volume 2, pages 423–429 (2001)Cite this article

Abstract

In defense of the host, the immune system must often raise an effective cytotoxic T lymphocyte (CTL) response from a small number of clonal precursors. The degree to which activation stimuli regulate the expansion and differentiation of naïve CTLs, however, remains unknown. Using an engineered antigen-presenting cell (APC) system that allows control over antigenic stimulation, we studied the signaling duration requirements for priming and clonal expansion of naïve CTLs. We found that naïve CTLs become committed after as little as 2 h of exposure to APCs and that their subsequent division and differentiation can occur without the need for further antigenic stimulation of the daughter cells, whether priming is in vitro or in vivo. These data show that after a brief interaction with stimulatory APCs, naïve CTLs initiate a program for their autonomous clonal expansion and development into functional effectors.

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Figure 1: Engineered APCs induce primary activation of OT-I cells.
Figure 2: A brief antigenic stimulation leads to rapid antigen-independent CTL expansion.
Figure 3: The antigenic stimulus leading to OT-I priming is not transferred to the second culture well.
Figure 4: Expansion kinetics of CTLs primed in vitro or in vivo.
Figure 5: Primed CTLs expand in vitro or in vivo in the absence of antigen.
Figure 6: Surface TCR reappears when CTLs are separated from APCs.
Figure 7: Development of effector function in the absence of antigen.

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Acknowledgements

We thank G. Palioungas, P. Houshmand, K. Banks and the staff of the LIAI animal facility for excellent care and screening of mice. We also thank F. Koning and E. Sercarz for critical evaluation of the manuscript. Supported by the American Cancer Society (to S. P. S.) and the Dutch Cancer Society (to M. J. B. v. S).

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Authors and Affiliations

  1. Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, 92121, CA, USA

    Marianne J. B. van Stipdonk, Edward E. Lemmens & Stephen P. Schoenberger

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Correspondence to Stephen P. Schoenberger.

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van Stipdonk, M., Lemmens, E. & Schoenberger, S. Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat Immunol 2, 423–429 (2001). https://doi.org/10.1038/87730

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