Towards estimating the true duration of dendritic cell interactions with T cells

被引:24
作者
Beltman, Joost B. [1 ]
Henrickson, Sarah E. [2 ,3 ]
von Andrian, Ulrich H. [2 ,3 ]
de Boer, Rob J. [1 ]
Maree, Athanasius F. M. [1 ]
机构
[1] Univ Utrecht, NL-3584 CH Utrecht, Netherlands
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
Cellular Potts Model; Censored data; Immunological synapse; T cell-DC interactions; T cell motility; Multi-photon microscopy; LYMPH-NODES; IN-VIVO; REAL-TIME; 2-PHOTON MICROSCOPY; B-CELLS; ACTIVATION; BEHAVIOR; TOLERANCE; MIGRATION; IMMUNITY;
D O I
10.1016/j.jim.2009.05.013
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
To initiate an adaptive immune response, T cells need to interact with dendritic cells (DCs), and the duration of these interactions plays an important role. In vitro and in vivo experiments have generally tried to estimate the required period of opportunity for T cell stimulation rather than the duration of individual T cell-DC interactions. Since the application of multi-photon microscopy (MPM) to living lymphoid tissues, the interactions between immune cells, as well as the duration thereof, can directly be observed in vivo. Indeed, long-lasting interactions between T cells and DCs were shown to be important for the onset of immune responses. However, because MPM imaging is typically restricted to experiments lasting 1 h, and because T cell-DC conjugates frequently move into and out of the imaged volume, it is difficult to estimate the true duration of interactions from MPM contact data. Here, we present a method to properly make such an estimate of (the average of) the distribution of contact durations. We validate the method by applying it to spatially explicit computer simulations where the true distribution of contact duration is known. Finally, we apply our analysis to a large experimental data set of T-DC contacts, and predict an average contact time of about three hours. However, we identify a mismatch between the experimental data and the model predictions, and investigate possible causes of the mismatch, including minor tissue drift during imaging experiments. We discuss in detail how future experiments can be optimized such that MPM contact data will be minimally affected by these factors. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:54 / 69
页数:16
相关论文
共 44 条
[1]   Imaging of germinal center selection events during affinity maturation [J].
Allen, Christopher D. C. ;
Okada, Takaharu ;
Tang, H. Lucy ;
Cyster, Jason G. .
SCIENCE, 2007, 315 (5811) :528-531
[2]   Natural killer cell behavior in lymph nodes revealed by static and real-time imaging [J].
Bajénoff, M ;
Breart, B ;
Huang, AYC ;
Qi, H ;
Cazareth, J ;
Braud, VM ;
Germain, RN ;
Glaichenhaus, N .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (03) :619-631
[3]   The strategy of T cell antigen-presenting cell encounter in antigen-draining lymph nodes revealed by imaging of initial T cell activation [J].
Bajénoff, M ;
Granjeaud, S ;
Guerder, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (05) :715-724
[4]   Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes [J].
Bajenoff, Marc ;
Egen, Jackson G. ;
Koo, Lily Y. ;
Laugier, Jean Pierre ;
Brau, Frederic ;
Glaichenhaus, Nicolas ;
Germain, Ronald N. .
IMMUNITY, 2006, 25 (06) :989-1001
[5]   Lymph node topology dictates T cell migration behavior [J].
Beltman, Joost B. ;
Maree, Athanasius F. M. ;
Lynch, Jennifer N. ;
Miller, Mark J. ;
de Boer, Rob J. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (04) :771-780
[6]   Spatial modelling of brief and long interactions between T cells and dendritic cells [J].
Beltman, Joost B. ;
Maree, Athanasius F. M. ;
de Boer, Rob J. .
IMMUNOLOGY AND CELL BIOLOGY, 2007, 85 (04) :306-314
[7]   Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy [J].
Bousso, P ;
Bhakta, NR ;
Lewis, RS ;
Robey, E .
SCIENCE, 2002, 296 (5574) :1876-1880
[8]   Cellular orchestration of T cell priming in lymph nodes [J].
Breart, Beatrice ;
Bousso, Philippe .
CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (04) :483-490
[9]   Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4 T cell-dendritic cell interaction [J].
Castellino, F ;
Huang, AY ;
Altan-Bonnet, G ;
Stoll, S ;
Scheinecker, C ;
Germain, RN .
NATURE, 2006, 440 (7086) :890-895
[10]   CD4 T cells integrate signals delivered during successive DC encounters in vivo [J].
Celli, S ;
Garcia, Z ;
Bousso, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (09) :1271-1278