Activation-induced accumulation of B and T lymphocyte attenuator at the immunological synapse in CD4+ T cells.
BTLA, a recently cloned coreceptor expressed on lymphocytes, negatively regulates cell activation by recruiting SHP-1/SHP-2. However, the mechanisms that regulate the intracellular localization of BTLA and its trafficking to the cell surface in T cells are still unknown. To determine the mechanisms that regulate the expression of BTLA on the surface of T cells, we examined the subcellular localization of BTLA in mouse T cells in a steady state, as well as upon activation by using a confocal laser-scanning microscopy. We found that BTLA was localized mainly in the Golgi apparatus and secretory lysosomes in resting CD4(+) T cells. We also found that intracellular BTLA was translocated to the cell surface and accumulated at the immunological synapse upon TCR stimulation. Furthermore, we found that the BTLA-HVEM interaction was required for the association of BTLA with lipid rafts. These results indicate that the surface expression of BTLA and its accumulation at the immunological synapse are tightly regulated by TCR and HVEM stimulation to deliver efficient inhibitory signals in the regulation of CD4(+) T cell activation.
Owada
Takayoshi
T
Departments of Allergy and Clinical Immunology, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan.
Watanabe
Norihiko
N
Oki
Mie
M
Oya
Yoshihiro
Y
Saito
Yasushi
Y
Saito
Takashi
T
Iwamoto
Itsuo
I
Murphy
Theresa L
TL
Murphy
Kenneth M
KM
Nakajima
Hiroshi
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D054992:Immunological Synapses / Q000187:drug effects / Q000276:immunology*; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C488868:BTLA protein, mouse; D007476:Ionophores; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium