Gap junctions between regulatory T cells and dendritic cells prevent sensitization of CD8(+) T cells.
BACKGROUND
Regulatory T (Treg) cells suppress the sensitization phase of experimental contact hypersensitivity (CHS) reactions when injected before hapten application.


OBJECTIVE
Our aim was to analyze the mechanisms by which Treg cells suppress the sensitization phase of CHS reactions.


METHODS
Treg cells were labeled with different fluorescent dyes and injected into naive mice directly before sensitization with the hapten 2,4,6-trinitro-1-chlorobenzene. Two days after sensitization, the lymphoid organs were analyzed for the presence of Treg cells and engagement of gap junctions with other cells. Dendritic cells (DCs) and effector CD8(+)T cells were isolated from the draining lymph nodes (LNs) of the differently treated groups, analyzed by using FACS for activation markers, and assessed for the T-cell stimulatory capacity of the DCs and the priming of effector T cells.


RESULTS
Only the LN-homing Treg cells suppressed the sensitization phase in CHS reactions by means of establishing gap junctions with DCs in the dLNs. This gap junctional intercellular communication led to downregulation of T-cell costimulatory molecules on the surface of the DCs, abrogating the priming, activation, and proliferation of hapten-specific CD8(+)T cells. Consequently, the ear-swelling response induced by challenge with the respective hapten was prevented.


CONCLUSIONS
Treg cells not only modulate ongoing CD4(+)T cell-mediated immune reactions at tissue sites but also abrogate the de novo induction of CD8(+)T cell-driven immune reactions by interfering with T-cell stimulatory activity of DCs through gap junctional intercellular communication.
Ring
Sabine
S
Department of Dermatology, University Hospital Heidelberg, Vossstrasse 11, 69115 Heidelberg, Germany. Sabine.Ring@med.uni-heidelberg.de
Karakhanova
Svetlana
S
Johnson
Theron
T
Enk
Alexander H
AH
Mahnke
Karsten
K
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D005434:Flow Cytometry; D017629:Gap Junctions / Q000502:physiology*; D006241:Haptens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D006241:Haptens