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The TNF–TNFR Family of Co-signal Molecules

  • Takanori SoEmail author
  • Naoto Ishii
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1189)

Abstract

Costimulatory signals initiated by the interaction between the tumor necrosis factor (TNF) ligand and cognate TNF receptor (TNFR) superfamilies promote clonal expansion, differentiation, and survival of antigen-primed CD4+ and CD8+ T cells and have a pivotal role in T-cell-mediated adaptive immunity and diseases. Accumulating evidence in recent years indicates that costimulatory signals via the subset of the TNFR superfamily molecules, OX40 (TNFRSF4), 4-1BB (TNFRSF9), CD27, DR3 (TNFRSF25), CD30 (TNFRSF8), GITR (TNFRSF18), TNFR2 (TNFRSF1B), and HVEM (TNFRSF14), which are constitutive or inducible on T cells, play important roles in protective immunity, inflammatory and autoimmune diseases, and tumor immunotherapy. In this chapter, we will summarize the findings of recent studies on these TNFR family of co-signaling molecules regarding their function at various stages of the T-cell response in the context of infection, inflammation, and cancer. We will also discuss how these TNFR co-signals are critical for immune regulation and have therapeutic potential for the treatment of T-cell-mediated diseases.

Keywords

4-1BB CD27 CD30 DR3 HVEM GITR OX40 TNFR2 TNFSF TNFRSF 

Abbreviations

APC

antigen-presenting cell;

CAR

chimeric antigen receptor

CMV

cytomegalovirus

CTL

cytotoxic T lymphocyte

CTLA-4

cytotoxic T-lymphocyte-associated protein-4

DC

dendritic cell

DcR3

decoy receptor 3

DR3

death receptor 3

EAE

experimental autoimmune encephalomyelitis

EBV

Epstein–Barr virus

GC

germinal center

GITR

glucocorticoid-induced TNFR family-related protein

GVHD

graft-versus-host disease

HPV

human papillomavirus

HVEM

herpesvirus entry mediator

ICOS

inducible T-cell costimulator

LCMV

lymphocytic choriomeningitis virus

LIGHT

homologous to lymphotoxins (LTs), inducible expression, which competes with herpes simplex virus glycoprotein D (HSV gD) for HVEM, a receptor expressed on T lymphocytes

mAb

monoclonal antibody

MAPK

mitogen-activated protein kinase

NF-κB

nuclear factor-kappa B

PD-1

programmed cell death-1

SLE

systemic lupus erythematosus

TCR

T-cell receptor

Tfh

T follicular helper

Th1

T-helper-1

Th17

T-helper-17

Th2

T-helper-2

Th9

T-helper-9

TL1A

TNF-like ligand 1A

TLR

Toll-like receptor

TNF

tumor necrosis factor

TNFR2

tumor necrosis factor receptor 2

TNFRSF

TNF receptor superfamily

TNFSF

TNF superfamily

TRAF

TNF receptor-associated factor

Treg cells

Foxp3+ CD25+ CD4+ regulatory T cells

Notes

Acknowledgments

This work was supported by JSPS KAKENHI Grant Numbers 24590571 (to T.S.), 15H04640 (to T.S.), 18H02572 (to T.S.), 24390118 (to N.I.), 15H04742 (to N.I.), and 16K15508 (to N.I.), as well as by grants from the Takeda Science Foundation (to T.S.), the Suzuken Memorial Foundation (to T.S.), the SENSHIN Medical Research Foundation (to T.S.), the Astellas Foundation for Research on Metabolic Disorders (to T.S.), the Yamaguchi Educational and Scholarship Foundation (to T.S.), and the Daiichi-Sankyo Foundation of Life Science (to N.I. and T.S.).

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan

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