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Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Nature volume 486, pages 545–548 (2012)Cite this article

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Abstract

Chemokines have a central role in regulating processes essential to the immune function of T cells1,2,3, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys4,5,6,7,8,9,10, and CXCL10 aids T cells in shortening the average time taken to find rare targets.

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Figure 1: Chemokine and chemokine receptor expression in the brain during chronic toxoplasmosis.
Figure 2: CXCL10 affects the CD8 + T-cell population and the control of parasite replication.
Figure 3: CD8 + T-cell migration tracks are consistent with generalized Lévy walks.
Figure 4: Generalized Lévy walks find targets more efficiently than random walks.

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Acknowledgements

This work was supported by grants from the National Institutes of Health AI-41158 (C.A.H.), AI-42334 (C.A.H.), EY-021314 (C.A.H.), T32-AI-055400 (T.H.H.), AI-081478 (T.H.H.), CA-069212 (A.D.L.), RNS-072298 (E.H.W.) and AI-090234 (B.J.); the National Science Foundation DMR-0520020 (E.J.B.) and DMR-1104637 (E.J.B. and A.J.L.); the state of Pennsylvania; Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research Grant 20592071 (K.N.); and the Ministry of Education, Culture, Sports, Science and Technology of Japan (K.N.). We acknowledge L. Zhang and the Penn Vet Imaging Facility for technical assistance.

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Authors and Affiliations

  1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 380 South University Avenue, Philadelphia, 19104, Pennsylvania, USA

    Tajie H. Harris, David A. Christian, Christoph Konradt, Elia D. Tait Wojno, Beena John & Christopher A. Hunter

  2. Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, 209 South 33rd Street, Philadelphia, Pennsylvania 19104, USA,

    Edward J. Banigan & Andrea J. Liu

  3. Department of Infection and Host Defense, Graduate School of Medicine, Chiba University 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan,

    Kazumi Norose

  4. Division of Biomedical Sciences, University of California-Riverside, Riverside, 92521, California, USA

    Emma H. Wilson

  5. The Centenary Institute, Newtown, 2042, New South Wales, Australia

    Wolfgang Weninger

  6. Discipline of Dermatology, Sydney Medical School, Sydney, 2006, New South Wales, Australia

    Wolfgang Weninger

  7. Division of Rheumatology, Center for Immunology and Inflammatory Diseases, Allergy and Immunology, Massachusetts General Hospital, Building 149, 13th Street, Room 8301, Charlestown, Massachusetts 02129, USA,

    Andrew D. Luster

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Contributions

T.H.H. and E.J.B. contributed equally to this work. T.H.H. performed the immunological in vivo and imaging studies and wrote the paper. E.J.B. performed analysis of T-cell migration and designed the mathematical model. K.N. and E.D.T.W. collected data. A.J.L. and C.A.H. were involved in study design and contributed equally. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Andrea J. Liu or Christopher A. Hunter.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-10, Supplementary Tables 1-3, a Supplementary Discussion, Supplementary Text and Data, additional references and legends for Supplementary Movies 1-3. (PDF 806 kb)

Supplementary Movie 1

This movie shows OT-IGFP migration in the brains of control mice - see the Supplementary Information file for full legend. (MOV 4645 kb)

Supplementary Movie 2

This movie shows OT-IGFP migration in the brains of anti-CXCL10-treated mice – see the Supplementary Information file for full legend. (MOV 3610 kb)

Supplementary Movie 3

This movie shows OT-IGFP migration in the brains of pertussis-toxin-treated mice – see the Supplementary Information file for full legend. (MOV 2458 kb)

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Harris, T., Banigan, E., Christian, D. et al. Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature 486, 545–548 (2012). https://doi.org/10.1038/nature11098

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