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Restoration of lymphoid organ integrity through the interaction of lymphoid tissue–inducer cells with stroma of the T cell zone

Nature Immunology volume 9, pages 667–675 (2008)Cite this article

Abstract

The generation of lymphoid microenvironments in early life depends on the interaction of lymphoid tissue–inducer cells with stromal lymphoid tissue–organizer cells. Whether this cellular interface stays operational in adult secondary lymphoid organs has remained elusive. We show here that during acute infection with lymphocytic choriomeningitis virus, antiviral cytotoxic T cells destroyed infected T cell zone stromal cells, which led to profound disruption of secondary lymphoid organ integrity. Furthermore, the ability of the host to respond to secondary antigens was lost. Restoration of the lymphoid microanatomy was dependent on the proliferative accumulation of lymphoid tissue–inducer cells in secondary lymphoid organs during the acute phase of infection and lymphotoxin α1β2 signaling. Thus, crosstalk between lymphoid tissue–inducer cells and stromal cells is reactivated in adults to maintain secondary lymphoid organ integrity and thereby contributes to the preservation of immunocompetence.

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Figure 1: Disruption and restoration of lymphoid organization during LCMV infection.
Figure 2: CTL-mediated lysis of T cell zone stromal cells in vitro.
Figure 3: Loss of T zone stromal cells in LCMV-infected mice.
Figure 4: Gene-expression patterns in LCMV-infected spleens.
Figure 5: Accumulation and proliferation of LTi cells in SLOs after LCMV infection.
Figure 6: Lymphoid organ reorganization is supported by LTi cells.
Figure 7: Interaction of LTi cells with stromal cells.

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Acknowledgements

We thank X.Y. Fu (University of Chicago) for providing soluble LTβR-hIg, and R.M. Zinkernagel (University of Zürich) for providing the VL4 hybridoma and the original LCMV WE stock. Supported by the Kanton of St. Gallen and the Swiss Life Foundation.

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Authors and Affiliations

  1. Research Department, Kantonal Hospital of St. Gallen, St. Gallen, 9007, Switzerland

    Elke Scandella, Beatrice Bolinger, Evelyn Lattmann, Simone Miller & Burkhard Ludewig

  2. Department of Biochemistry, University of Lausanne, Epalinges, 1066, Switzerland

    Stéphanie Favre & Sanjiv A Luther

  3. Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, 10016, New York, USA

    Dan R Littman

  4. Developmental Immunobiology, Center for Biomedicine, University of Basel, Basel, 4058, Switzerland

    Daniela Finke

  5. Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Tobias Junt

  6. Novartis Institutes for BioMedical Research, Vienna, 1235, Austria

    Tobias Junt

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  1. Elke Scandella
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Contributions

B.L. directed the study and wrote the manuscript; E.S. designed the study, did experiments and wrote the manuscript; T.J. did research and contributed to manuscript writing; E.L. contributed to low-density array analysis and real-time PCR; E.L., B.B., S.M., D.F. and S.F. did research; S.A.L. contributed to data analysis and provided reagents; and D.R.L. provided Rorc−/− mice.

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Correspondence to Burkhard Ludewig.

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T.J. is an employee of the Novartis Institutes for BioMedical Research.

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Scandella, E., Bolinger, B., Lattmann, E. et al. Restoration of lymphoid organ integrity through the interaction of lymphoid tissue–inducer cells with stroma of the T cell zone. Nat Immunol 9, 667–675 (2008). https://doi.org/10.1038/ni.1605

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