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Visualizing the generation of memory CD4 T cells in the whole body

Nature volume 410, pages 101–105 (2001)Cite this article

Abstract

It is thought that immunity depends on naïve CD4 T cells that proliferate in response to microbial antigens1,2,3,4, differentiate into memory cells that produce anti-microbial lymphokines5,6, and migrate to sites of infection7,8. Here we use immunohistology to enumerate individual naïve CD4 T cells, specific for a model antigen, in the whole bodies of adult mice. The cells resided exclusively in secondary lymphoid tissues, such as the spleen and lymph nodes, in mice that were not exposed to antigen. After injection of antigen alone into the blood, the T cells proliferated, migrated to the lungs, liver, gut and salivary glands, and then disappeared from these organs. If antigen was injected with the microbial product lipopolysaccharide, proliferation and migration were enhanced, and two populations of memory cells survived for months: one in the lymph nodes that produced the growth factor interleukin-2, and a larger one in the non-lymphoid tissues that produced the anti-microbial lymphokine interferon-γ. These results show that antigen recognition in the context of infection generates memory cells that are specialized to proliferate in the secondary lymphoid tissues or to fight infection at the site of microbial entry.

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Figure 1: Detection of antigen-specific T cells in whole-body sections.
Figure 2: Tissue distribution of antigen-specific T cells during a primary immune response.
Figure 3: Quantification of antigen-specific T cells.
Figure 4: Lymphokine production by antigen-specific CD4 T cells.

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Acknowledgements

We thank J. Walter for technical assistance; D. Mueller, S. Jameson, M. Mescher, A. Haase, P. Southern, R. A. Reinhardt and K. Hogquist for discussions; L. Lefrancois for supplying OT-II mice; and Gerald Sedgewick for help with image analysis. Supported by grants from the NIH (M.K.J., A.K., R.M. and R.L.R.), the Cancer Research Institute (T.Z.), and the Howard Hughes Medical Institute (A.K.).

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Authors and Affiliations

  1. Department of Microbiology,

    R. Lee Reinhardt, Rebecca Merica, Traci Zell & Marc K. Jenkins

  2. Department of Medicine, Center for Immunology, University of Minnesota Medical School, MMC 334, 420 Delaware Street S.E., Minneapolis, 55455, Minnesota, USA

    Alexander Khoruts

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Correspondence to Marc K. Jenkins.

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Reinhardt, R., Khoruts, A., Merica, R. et al. Visualizing the generation of memory CD4 T cells in the whole body. Nature 410, 101–105 (2001). https://doi.org/10.1038/35065111

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