Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity (original) (raw)

Nature Immunology volume 5, pages 1235–1242 (2004)Cite this article

Abstract

Induction of immunity and peripheral tolerance requires contacts between antigen-bearing dendritic cells (DCs) and cognate T cells. Using real-time two-photon microscopy, we have analyzed the dynamics of CD8+ T cells in lymph nodes during the induction of antigen-specific immunity or tolerance. At 15–20 h after the induction of immunity, T cells stopped moving and established prolonged interactions with DCs. In tolerogenic conditions, despite effective initial T cell activation and proliferation, naive T cells remained motile and established serial brief contacts with multiple DCs. Thus, stable DC–T cell interactions occur during the induction of priming, whereas brief contacts may contribute to the induction of T cell tolerance.

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Acknowledgements

We thank O. Lantz, C. Théry, W. Ferlin and A.M. Lennon-Dumenil for critical reading of the manuscript, and B. Combadière and A. Boissonnas for the gift of mice and for discussions. Supported by Institut National de la Santé et de la Recherche Médicale, Institut Curie and Ligue Nationale Contre le Cancer; S.H. was supported by a fellowship from Ligue Nationale Contre le Cancer.

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Author notes

  1. Laura Bonifaz
    Present address: Research Unit on Autoimmune Diseases, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
  2. Stéphanie Hugues and Luc Fetler: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale U365, Immunité et Cancer, Institut Curie, 26 rue d'Ulm, Paris, F-75248, Cedex 05, France
    Stéphanie Hugues & Sebastian Amigorena
  2. Centre National de la Recherche Scientifique UMR 168, Laboratoire de Physico-Chimie Curie, Institut Curie, 26 rue d'Ulm, Paris, F-75248, Cedex 05, France
    Luc Fetler & François Amblard
  3. Laboratory of Cellular Physiology and Immunology, Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, 10021, New York, USA
    Laura Bonifaz
  4. Institut National de la Santé et de la Recherche Médicale U520, Biologie Cellulaire de l'Immunité Tumorale, Institut Curie, 26 rue d'Ulm, Paris, F-75248, Cedex 05, France
    Julie Helft

Authors

  1. Stéphanie Hugues
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  2. Luc Fetler
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  3. Laura Bonifaz
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  4. Julie Helft
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  5. François Amblard
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  6. Sebastian Amigorena
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Corresponding author

Correspondence toSebastian Amigorena.

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Supplementary information

Supplementary Fig. 1

Specific labelling of LN resident DCs. (PDF 235 kb)

Supplementary Fig. 2

Antigen re-challenge does not prolong T cell arrest. (PDF 42 kb)

Supplementary Fig. 3

Similar efficiency of antigen presentation by DCs purified 8-10 h, 15-20 h or 30-48 h after induction of priming or tolerance. (PDF 44 kb)

Supplementary Fig. 4

T cells interact briefly with DCs purified after αDEC205-OVA injection. (PDF 435 kb)

Supplementary Fig. 5

Duration of category II and category III T cell arrests (s). (PDF 455 kb)

Supplementary Video 1

Time-lapse TPLSM video (acceleration 200×; 100×100 μm) showing Alexa488-labelled DCs, after labelling of resident DCs in intact LNs. (AVI 2118 kb)

Supplementary Video 2

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing CMTMR-labelled OT-1 cells (red) crawling in LN from untreated mice. Most T cells do not interact with DCs (green). (AVI 4095 kb)

Supplementary Video 3

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing dynamic and transient interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice co-injected 8-10 h earlier with αDEC205-OVA and LPS. (AVI 4176 kb)

Supplementary Video 4

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing long-lasting interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice co-injected 15-20 h earlier with αDEC205-OVA and CD40 antibody. (AVI 2094 kb)

Supplementary Video 5

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing dynamic and transient interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice co-injected 30-48 h earlier with αDEC205-OVA and LPS. (AVI 4192 kb)

Supplementary Video 6

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing long-lasting interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice injected 20 h earlier with αDEC205-OVA plus CD40 antibody, and adoptively transferred 10 h earlier with T cells. (AVI 4224 kb)

Supplementary Video 7

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing dynamic and transient interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice injected 30 h earlier with αDEC205-OVA plus CD40 antibody, and adoptively transferred 20 h earlier with T cells. (AVI 4206 kb)

Supplementary Video 8

Time-lapse video-microscopy (acceleration 52×; 65×65 μm) showing interactions between naive OT-1 cells and DCs purified from mice co-injected 8-10 h earlier with αDEC205-OVA and LPS. Note that the T cell on the left of the movie interacts transiently with three different DCs. (AVI 3439 kb)

Supplementary Video 9

Time-lapse video-microscopy (acceleration 52×; 65×65 μm) showing interactions between naive OT-1 cells and DCs purified from mice co-injected 15-20 h earlier with αDEC205-OVA and LPS. Note that most T cells are engulfed by DCs. (AVI 2638 kb)

Supplementary Video 10

Time-lapse TPLSM video (acceleration 200×; 280×280×18 μm (x, y, z)) showing dynamic and transient interactions between CMTMR-labelled OT-1 cells (red) and DCs (green) in LN from mice co-injected 15-20 h earlier with αDEC205-OVA. (AVI 2033 kb)

Supplementary Video 11

Representative time-lapse TPLSM video (acceleration 200×; 55×55×18 μm (x, y, z)) showing T cells (red) that did not arrest during the observation period (category I). (AVI 247 kb)

Supplementary Video 12

Representative time-lapse TPLSM video (acceleration 200×; 55×55×18 μm (x, y, z)) showing T cells (red) that showed multiple pauses or constrained migration at multiple points in the proximity of several DCs along their trajectory (category II) or that remained constrained throughout the imaging period in the proximity of the same DC (category III). (AVI 285 kb)

Supplementary Video 13

Representative time-lapse TPLSM video (acceleration 200×; 55×55×18 μm (x, y, z)) showing T cells (red) arrested (instantaneous velocity < 2 μm/min) in close proximity of a DC (green) during the whole observation period (15 or 30 min), (category IV). (AVI 183 kb)

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Hugues, S., Fetler, L., Bonifaz, L. et al. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity.Nat Immunol 5, 1235–1242 (2004). https://doi.org/10.1038/ni1134

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