Structure and duration of contact between dendritic cells and T cells are controlled by T cell activation state.
The adaptive immune response is initiated when naive T cells interact with dendritic cells (DC). However, the physicodynamics as well as the molecules that constitute the contact plane (immunological synapse) between DC and T cells are not well understood. We show here that for the formation of stable conjugates, T cells need to be preactivated by DC in a CD80/86- and antigen dose-dependent manner. When activated, T cells induce cytoskeletal reorganization within DC via CD40-CD40L signaling. Polarization of the actin and fascin cytoskeleton in DC is associated with sustained DC-T cell contacts, strong T cell proliferation and a Th1 response. Organized contact planes with clearly separated patches containing TCR or CD11a are also formed. Thus, DC-T cell interactions take place in a sequential, interdependent fashion: first, DC "license" naive T cells to engage DC in an antigen dose- and CD80/86-dependent fashion. Then, these preactivated T cells induce cytoskeletal reorientation in DC, resulting in sustained DC-T cell contacts and subsequent T cell activation. These results demonstrate that T cells control the mode of interaction based on information gathered from DC.
Rothoeft
Tobias
T
Children's Hospital of the Ruhr-University-Bochum, Germany.
Balkow
Sandra
S
Krummen
Mathias
M
Beissert
Stefan
S
Varga
Georg
G
Loser
Karin
K
Oberbanscheidt
Pia
P
van den Boom
Frank
F
Grabbe
Stephan
S
D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013997:Time Factors
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse