OX40-OX40 ligand interaction in T-cell-mediated immunity and immunopathology.
T-cell activation is mediated not only by antigen stimulation through T-cell receptors but also by costimulatory signals through costimulatory molecules. Among several costimulatory molecules, the tumor necrosis factor (TNF) receptor family member OX40 plays a key role in the survival and homeostasis of effector and memory T cells. According to the conventional understanding of OX40 costimulation, an interaction between OX40 and OX40 ligand (OX40L) occurs when activated T cells bind to professional antigen-presenting cells (APCs). The T-cell functions, including cytokine production, expansion, and survival, are then enhanced by the OX40 costimulatory signals. Over the last half-decade, evidence has accumulated that OX40 signals are critical for controlling the function and differentiation of Foxp3(+) regulatory T cells, indicating a new aspect of OX40-mediated autoimmunity. Furthermore, the expression of OX40L by mast cells was shown to be important for controlling inflammation through regulatory T-cell function. Besides the essential role played by OX40 signaling in generating memory CD4 T cells, recent reports show that it also has a unique role in generating memory CD8 T cells. In addition, recent genome-wide association studies have identified single-nucleotide polymorphisms of the OX40L and OX40 genes that are related to cardiovascular diseases and SLE, providing direct evidence for the involvement of the OX40-OX40L interaction in human diseases. Here, we review recent progress on how the OX40-OX40L interaction regulates T-cell tolerance, peripheral T-cell homeostasis, and T-cell-mediated inflammatory diseases.
Ishii
Naoto
N
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Takahashi
Takeshi
T
Soroosh
Pejman
P
Sugamura
Kazuo
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D053278:OX40 Ligand / Q000378:metabolism*; D053262:Receptors, OX40 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015851:Interleukin-7; D053278:OX40 Ligand; D053262:Receptors, OX40; D016212:Transforming Growth Factor beta