Intravital imaging reveals distinct dynamics for natural killer and CD8(+) T cells during tumor regression.
Recognition of NKG2D ligands by natural killer (NK) cells plays an important role during antitumoral responses. To address how NKG2D engagement affects intratumoral NK cell dynamics, we performed intravital microscopy in a Rae-1β-expressing solid tumor. This NKG2D ligand drove NK cell accumulation, activation, and motility within the tumor. NK cells established mainly dynamic contacts with their targets during tumor regression. In sharp contrast, cytotoxic T lymphocytes (CTLs) formed stable contacts in tumors expressing their cognate antigen. Similar behaviors were observed during effector functions in lymph nodes. In vitro, contacts between NK cells and their targets were cytotoxic but did not elicit sustained calcium influx nor adhesion, whereas CTL contact stability was critically dependent on extracellular calcium entry. Altogether, our results offer mechanistic insight into how NK cells and CTLs can exert cytotoxic activity with remarkably different contact dynamics.
Deguine
Jacques
J
Institut Pasteur, Dynamics of Immune Responses Unit, 75015 Paris, France. jacques.deguine@pasteur.fr
Breart
Béatrice
B
Lemaître
Fabrice
F
Di Santo
James P
JP
Bousso
Philippe
P
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology; D009369:Neoplasms / Q000276:immunology*
C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491218:Raet1b protein, mouse; D002118:Calcium