B and T lymphocyte attenuator is highly expressed on CMV-specific T cells during infection and regulates their function.
B and T lymphocyte attenuator (BTLA), like its relative programmed cell death-1 (PD-1), is a receptor that negatively regulates murine T cell activation. However, its expression and function on human T cells is currently unknown. We report in this study on the expression of BTLA in human T cell subsets as well as its regulation on virus-specific T cells during primary human CMV infection. BTLA is expressed on human CD4(+) T cells during different stages of differentiation, whereas on CD8(+) T cells, it is found on naive T cells and is progressively downregulated in memory and differentiated effector-type cells. During primary CMV infection, BTLA was highly induced on CMV-specific CD8(+) T cells immediately following their differentiation from naive cells. After control of CMV infection, BTLA expression went down on memory CD8(+) cells. Engagement of BTLA by mAbs blocked CD3/CD28-mediated T cell proliferation and Th1 and Th2 cytokine secretion. Finally, in vitro blockade of the BTLA pathway augmented, as efficient as anti-PD-1 mAbs, allogeneic as well as CMV-specific CD8(+) T cell proliferation. Thus, our results suggest that, like PD-1, BTLA provides a potential target for enhancing the functional capacity of CTLs in viral infections.
Serriari
Nacer-Eddine
NE
Institut National de Santé et de Recherche Médicale Unité Mixte de Recherche 891, Institut Paoli Calmettes, Université de Méditerranée, Infrastructures en Biologie Sante et Agronomie Cancer Immunomonitoring Platform, Institut Fédératif de Recherche 137, Marseille, France.
Gondois-Rey
Françoise
F
Guillaume
Yves
Y
Remmerswaal
Ester B M
EB
Pastor
Sonia
S
Messal
Nassima
N
Truneh
Alemseged
A
Hirsch
Ivan
I
van Lier
René A W
RA
Olive
Daniel
D
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000821:virology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C482586:BTLA protein, human; D018984:Epitopes, T-Lymphocyte; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic