A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.
For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen matrices as structural scaffold, we directly compared the kinetics of T-cell engagement and activation by functionally major APC types, ie, dendritic cells (DCs) and resting or activated B cells. Resting B cells engaged T cells in long-lived (several hours), adhesive, and leukocyte function-associated antigen-1 (LFA-1)-dependent conjugates in 3-D collagen as well as in intact lymph nodes in vivo. DCs and preactivated B cells, however, supported predominantly dynamic, short-lived (minutes), and sequential contacts to T cells that were dependent on high cytoskeletal activity of the APCs but could not be inhibited by anti-LFA-1 treatment. Naive T cells were most strongly activated by DCs and activated B cells, whereas resting B cells were 100-fold less efficient to induce T-cell proliferation. Thus, in the same 3-D environment, naive T cells respond with a spectrum of different interaction modes dependent on the type and activation state of the APCs. Thereby, more dynamic interaction kinetics is positively correlated with higher T-cell priming efficiency.
Gunzer
Matthias
M
German Research Centre for Biotechnology, Junior Research Group Immunodynamics, Mascheroder Weg 1, 38124 Braunschweig, Germany. mgunzer@gbf.de
Weishaupt
Carsten
C
Hillmer
Anja
A
Basoglu
Yasmin
Y
Friedl
Peter
P
Dittmar
Kurt E
KE
Kolanus
Waldemar
W
Varga
Georg
G
Grabbe
Stephan
S
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002645:Chickens; D003094:Collagen; D003599:Cytoskeleton / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016169:Lymphocyte Function-Associated Antigen-1; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin; D003094:Collagen