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Table 2 Tumor necrosis factor/tumor necrosis factor receptor family members and functions

From: Immune checkpoint receptors in regulating immune reactivity in rheumatic disease

Molecule

Expression

Ligand/receptor

Function

DR3

Lymphocytes

Tumor necrosis factor-like cytokine 1A (TL1A) expressed on APCs [4]

Delivers a co-inhibitory signal, induces cell survival, prevents apoptosis [4],[5]

4-1BB/CD137

Activated T cells, Tregs, DCs and B cells

4-1BB ligand on DCs and B cells [6]

4-1BB induces CD8+ T-cell, NK T-cell and B-cell survival [6]

   

Signaling back via 4-1BB ligand induces monocyte activation [6]

OX40/CD134

Activated T cells

OX40 ligand/CD252 on B cells, endothelial cells, DCs and macrophages

OX40 increases CD4+ T-cell survival/effector function [6]

   

OX40 impacts immunoregulation by reducing interleukin-10 production by Tr1 and CD4+ Tregs [6]

CD27

Naïve T-cells, memory B cells, NK T cells, NK cells [6]

CD70 on activated lymphocytes and DCs

CD27-CD70 signaling on B cells propagates germinal center formation and plasma cell activities

   

Signaling on T cells results in proliferation and cytokine production [6]

CD40

B cells

CD154/CD40 ligand on T cells, T follicular helper cells, endothelial and epithelial cells, B cells or APCs [7]

CD154+ T cells permit germinal center formation

   

Signaling via CD40 on B cells induces B-cell differentiation, isotype switching and proliferation [7]

   

Signaling via CD40 on APCs, increases CD80 and CD86 expression [7]

  1. APC, antigen presenting cell; DC, dendritic cell; NK, natural killer; Treg, regulatory T cell.