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Two‐photon imaging of effector T‐cell behavior: lessons from a tumor model
Author(s) -
Ng Lai Guan,
Mrass Paulus,
Kinjyo Ichiko,
Reiner Steven L.,
Weninger Wolfgang
Publication year - 2008
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2008.00596.x
Subject(s) - cytotoxic t cell , effector , immunological synapse , biology , context (archaeology) , microbiology and biotechnology , immune system , tumor microenvironment , t cell , lytic cycle , immunology , t cell receptor , in vitro , paleontology , biochemistry , virus
Summary: Recent advances in two‐photon microscopy have provided a new way of visualizing the behavior of fluorescently tagged cells within their natural microenvironment. This technology has allowed for generating a detailed picture of the cellular interaction dynamics operant in the activation of T cells and B cells during primary immune responses within secondary lymphoid organs. In contrast, relatively little is known about the migratory and interactive behavior of effector T cells within peripheral organs. We have recently developed a two‐photon microscopy model that enables tracking of cytotoxic T cells within tumors. We have demonstrated that tumor‐infiltrating T lymphocytes (TILs) follow random migratory paths and that their migratory properties depend on signals from the T‐cell receptor. We further showed that TILs underwent short‐ and long‐term interactions with tumor cells as well as macrophages. Recently, we succeeded in dynamic imaging of the distribution of fluorescently tagged molecules within TILs at subcellular resolution, which will be instrumental for defining the composition of the lytic synapse as well as the targeted release of cytotoxic granules by these cells. The purpose of this review is to put our findings into the context of the current literature and to point out the molecular cues mediating effector T‐cell function as candidates for future investigation.