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The TNF–TNFR Family of Co-signal Molecules

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Co-signal Molecules in T Cell Activation

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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

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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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Authors and Affiliations

  1. Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takanori So & Naoto Ishii

  2. Laboratory of Molecular Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Takanori So

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  1. Takanori So
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  2. Naoto Ishii
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Correspondence to Takanori So .

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Editors and Affiliations

  1. Department of Molecular Immunology Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

    Miyuki Azuma

  2. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan

    Hideo Yagita

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So, T., Ishii, N. (2019). The TNF–TNFR Family of Co-signal Molecules. In: Azuma, M., Yagita, H. (eds) Co-signal Molecules in T Cell Activation. Advances in Experimental Medicine and Biology, vol 1189. Springer, Singapore. https://doi.org/10.1007/978-981-32-9717-3_3

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