ltration and elimination of a solid tumor

JEM © The Rockefeller University Press $15.00 Vol. 204, No. 2, February 19, 2007 345–356 www.jem.org/cgi/doi/10.1084/jem.20061890 345 T cell–mediated immune responses require the active migration of T cells in tissues and the establishment of specifi c cell–cell contacts with other cell types. T cell migration was analyzed intravitally in the last few years using noninvasive two-photon microscopy (1–3). In lymph nodes, T lymphocytes move using an “ameboid”like migration mode and display extremely high instantaneous velocities (up to 25 μm/min) (4, 5) compared with DCs or tumor cells (6, 7). The resulting high mean velocities allow naive T cells to “scan” high numbers of DCs seeking for their MHC-peptide ligands (8, 9). Once a specifi c ligand was encountered, T cells stop their migration and establish antigen-specifi c contacts with DCs. The duration of these contacts is determined by the maturation state of the interacting DCs and the eventual presence of regulatory T cells. In most experimental systems, long lasting (hours) contacts occurred during the induction of eff ective priming (4, 5, 9), whereas short interactions (minutes) were observed in tolerogenic conditions (10, 11) or in the presence of regulatory T cells (12, 13). Shakar et al. (14), however, only found modest diff erences in the mobility of CD4+ T cells during the induction of priming and tolerance. During antiviral, antitumor, or autoimmune responses, for example, diff erentiated eff ector T cells migrate in nonlymphoid tissues to interact with target cells. Similar to lymph nodes, eff ector T cell migration in rat spinal cord sections during experimental autoimmune encephalomyelitis displays “ameboid” characteristics and high mean velocities, showing antigen-specifi c arrests upon autoantigen recognition within the spinal cord (15). Few studies also analyzed the eff ector phases of immune responses by NK T cells or NK cells (16, 17). The killing of target cells by cytotoxic T lymphocytes was recently imaged in lymph nodes. Regulatory T cells were thus shown to reduce the killing effi ciency of CTLs by interfering with the polarized secretion of cytotoxic granules (18). The traffi cking of CD8+ cytotoxic T cells in tumorbearing mice was analyzed recently using magnetic resonance or positron-emission In vivo imaging of cytotoxic T cell infi ltration and elimination of a solid tumor