Intravital Imaging Reveals Distinct Dynamics for Natural Killer and CD8+ T Cells during Tumor Regression

被引:116
作者
Deguine, Jacques [1 ,2 ]
Breart, Beatrice [1 ,2 ]
Lemaitre, Fabrice [1 ,2 ]
Di Santo, James P. [3 ]
Bousso, Philippe [1 ,2 ]
机构
[1] Inst Pasteur, Dynam Immune Responses Unit, F-75015 Paris, France
[2] INSERM, U668, Equipe Avenir, F-75015 Paris, France
[3] Inst Pasteur, INSERM, U668, Innate Immun Unit, F-75015 Paris, France
关键词
ACTIVATING NKG2D RECEPTOR; NK CELLS; IN-VIVO; INHIBITORY RECEPTOR; IMMUNE-SYSTEM; TARGET-CELLS; IFN-GAMMA; LIGANDS; RECOGNITION; CYTOTOXICITY;
D O I
10.1016/j.immuni.2010.09.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta-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
引用
收藏
页码:632 / 644
页数:13
相关论文
共 46 条
[1]   Dynamic behavior of NK cells during activation in lymph nodes [J].
Beuneu, Helene ;
Deguine, Jacques ;
Breart, Beatrice ;
Mandelboim, Ofer ;
Di Santo, James P. ;
Bousso, Philippe .
BLOOD, 2009, 114 (15) :3227-3234
[2]   Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment [J].
Bhakta, NR ;
Oh, DY ;
Lewis, RS .
NATURE IMMUNOLOGY, 2005, 6 (02) :143-151
[3]   Serial Killing of Tumor Cells by Human Natural Killer Cells - Enhancement by Therapeutic Antibodies [J].
Bhat, Rauf ;
Watzl, Carsten .
PLOS ONE, 2007, 2 (03)
[4]   In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor [J].
Boissonnas, Alexandre ;
Fetler, Luc ;
Zeelenberg, Ingrid S. ;
Hugues, Stphanie ;
Amigorena, Sebastian .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) :345-356
[5]   Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice [J].
Breart, Beatrice ;
Lemaitre, Fabrice ;
Celli, Susanna ;
Bousso, Philippe .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (04) :1390-1397
[6]   The NKG2D receptor: immunobiology and clinical implications [J].
Burgess, Steven J. ;
Maasho, Kerima ;
Masilamani, Madhan ;
Narayanan, Sriram ;
Borrego, Francisco ;
Coligan, John E. .
IMMUNOLOGIC RESEARCH, 2008, 40 (01) :18-34
[7]   Adhesion to target cells is disrupted by the killer cell inhibitory receptor [J].
Burshtyn, DN ;
Shin, J ;
Stebbins, C ;
Long, EO .
CURRENT BIOLOGY, 2000, 10 (13) :777-780
[8]   Two-photon tissue imaging: Seeing the immune system in a fresh light [J].
Cahalan, MD ;
Parker, I ;
Wei, SH ;
Miller, MJ .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (11) :872-880
[9]   Visualizing CTL/melanoma cell interactions: multiple hits must be delivered for tumour cell annihilation [J].
Caramalho, Iris ;
Faroudi, Mustapha ;
Padovan, Elisabetta ;
Mueller, Sabina ;
Valitutti, Salvatore .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2009, 13 (9B) :3834-3846
[10]   Phospholipase C-γ2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells [J].
Caraux, A ;
Kim, N ;
Bell, SE ;
Zompi, S ;
Ranson, T ;
Lesjean-Pottier, S ;
Garcia-Ojeda, ME ;
Turner, M ;
Colucci, F .
BLOOD, 2006, 107 (03) :994-1002