Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells.
Co-signal receptors provide crucial activating or attenuating signals for T cells. The B and T lymphocyte attenuator (BTLA/CD272) is a third member of co-inhibitory receptors, which belongs to the CD28 immunoglobulin-superfamily. Using monoclonal antibodies (mAbs) against human BTLA, we show that BTLA is constitutively expressed on most CD4+ and CD8+ T cells and its expression progressively decreases upon T cell activation. Polarized Th1 and Th2 cells contained both BTLA-positive and BTLA-negative populations, but the extended culture diminished BTLA expression. Cross-linking BTLA with an agonistic mAb inhibited T cell proliferation and the production of the cytokines IFN-gamma and IL-10 in response to anti-CD3 stimulation. BTLA-mediated inhibition of T cell activation occurred during both primary CD4+ T cell responses and secondary CD4+ and CD8+ T cell responses, suggesting that BTLA ligation sends a constitutive "off" signal to T cells and thus might play an important role in the maintenance of T cell tolerance.
Otsuki
Noriko
N
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
Kamimura
Yousuke
Y
Hashiguchi
Masaaki
M
Azuma
Miyuki
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D011971:Receptors, Immunologic / Q000819:agonists / Q000032:analysis* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; C482586:BTLA protein, human; D017252:CD3 Complex; D011971:Receptors, Immunologic; D016753:Interleukin-10; D007371:Interferon-gamma