LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming.
A key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function-associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the αL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1-interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely with antigen-specific T-cell proliferation, generation of T-helper 1 cells, and immune responses leading to delayed-type hypersensitivity. We could revert normal interaction time and T-cell proliferation to wild-type levels by inhibition of active LFA-1 on DCs. Our data further suggest that cytohesin-1-interacting protein might be responsible for controlling LFA-1 deactivation on mature DCs. In summary, our findings indicate that LFA-1 on DCs needs to be in an inactive state to ensure optimal T-cell activation and suggest that regulation of LFA-1 activity allows DCs to actively control antigen-driven T-cell proliferation and effective immune responses.
Department of Dermatology, Johannes-Gutenberg-Universität Mainz, Mainz, Germany.
Sandra
S
Balkow
Stefanie
S
Heinz
Patricia
P
Schmidbauer
Waldemar
W
Kolanus
Bernhard
B
Holzmann
Stephan
S
Grabbe
Melanie
M
Laschinger
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034622:RNA Interference; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; C513660:Cybr protein, mouse; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1