Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy

Mark J. Miller, Sindy H. Wei, Michael D. Cahalan, Ian Parker

Research output: Contribution to journalArticlepeer-review

396 Scopus citations


The recirculation of T cells between the blood and secondary lymphoid organs requires that T cells are motile and sensitive to tissue-specific signals. T cell motility has been studied in vitro, but the migratory behavior of individual T cells in vivo has remained enigmatic. Here, using intravital two-photon laser microscopy, we imaged the locomotion and trafficking of naïve CD4+ T cells in the inguinal lymph nodes of anesthetized mice. Intravital recordings deep within the lymph node showed T cells flowing rapidly in the microvasculature and captured individual homing events. Within the diffuse cortex, T cells displayed robust motility with an average velocity of ≈11 μm·min-1 T cells cycled between states of low and high motility roughly every 2 min, achieving peak velocities >25 μm·min-1. An analysis of T cell migration in 3D space revealed a default trafficking program analogous to a random walk. Our results show that naïve T cells do not migrate collectively, as they might under the direction of pervasive chemokine gradients. Instead, they appear to migrate as autonomous agents, each cell taking an independent trafficking path. Our results call into question the role of chemokine gradients for basal T cell trafficking within T cell areas and suggest that antigen detection may result from a stochastic process through which a random walk facilitates contact with antigen-presenting dendritic cells.

Original languageEnglish
Pages (from-to)2604-2609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Mar 4 2003


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