In Vivo Imaging of T Cell Priming

Sci. Signal., 25 March 2008
Vol. 1, Issue 12, p. pt2
DOI: 10.1126/stke.112pt2

In Vivo Imaging of T Cell Priming

  1. Sarah E. Henrickson1,
  2. Thorsten R. Mempel1,
  3. Irina B. Mazo1,
  4. Bai Liu2,
  5. Maxim N. Artyomov3,
  6. Huan Zheng4,
  7. Antonio Peixoto1,
  8. Michael Flynn1,
  9. Balimkiz Senman1,
  10. Tobias Junt1,
  11. Hing C. Wong2,
  12. Arup K. Chakraborty3,4,5, and
  13. Ulrich H. von Andrian1,*
  1. 1Department of Pathology and the Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
  2. 2Altor BioScience Corporation, 2810 North Commerce Parkway, Miramar, FL 33025, USA.
  3. 3Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  4. 4Department of Chemistry, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  5. 5Department of Biological Engineering, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  1. *Presenter and corresponding author. E-mail, uva{at}hms.harvard.edu
A presentation from the 11th Joint Meeting of the Signal Transduction Society (STS), Signal Transduction: Receptors, Mediators and Genes, Weimar, Germany, 1 to 3 November 2007.

Abstract

The rules by which naïve T cells decide whether and how to respond to antigenic stimuli are incompletely understood. Using multiphoton intravital microscopy (MP-IVM) in lymph nodes (LNs), we have shown that CD8+ T cells are primed by antigen-presenting dendritic cells (DCs) in three consecutive phases. During phase one, T cells undergo brief serial contacts with many DCs for several hours after homing into the LNs. Subsequently, during phase two, T cells engage in prolonged stable interactions with DCs. Finally, in the third phase, T cells return to transient interactions with DCs as they begin to proliferate and eventually leave the LNs. We have examined the influence of antigen dose on the duration of phase one by systematically varying both the number of cognate peptide–major histocompatability (pMHC) complexes per DC and the density of cognate pMHC complex–presenting DCs per LN. The duration of phase one and the kinetics of CD8+ T cell activation were inversely correlated with both parameters. Very few pMHC complexes were needed for full T cell activation and effector differentiation. Furthermore, there was a sharp threshold of antigen dose below which T cells did not transition to phase two but continued to migrate until they exited the LN, unactivated. The stability of peptide binding to MHC was a critical determinant of this threshold antigen dose in vivo. Our results suggest an integrative mechanism that allows T cells to reach an informed decision about whether to respond, based on the overall antigen dose encountered.

Citation:

S. E. Henrickson, T. R. Mempel, I. B. Mazo, B. Liu, M. N. Artyomov, H. Zheng, A. Peixoto, M. Flynn, B. Senman, T. Junt, H. C. Wong, A. K. Chakraborty, and U. H. von Andrian, In Vivo Imaging of T Cell Priming. Sci. Signal. 1, pt2 (2008).

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High-resolution, noninvasive longitudinal live imaging of immune responses
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