CD134
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Location (UCSC) | Chr 1: 1.21 – 1.21 Mb | n/a | |||||||
PubMed search | [2] | [3] |
View/Edit Human | View/Edit Mouse |
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the
OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28
, expression of OX40 is delayed and of fourfold lower levels.
Function
OX40 has no effect on the proliferative abilities of
Th2 mediated reactions in vivo
.
OX40 binds
CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF3 DN defect was partially overcome by CTLA-4 blockade in vivo. TRAF3 may be linked to OX40-mediated memory T cell
expansion and survival, and point to the down-regulation of CTLA-4 as a possible control element to enhance early T cell expansion through OX40 signaling.
Clinical significance
OX40 has been implicated in the
H5N1 bird flu.[citation needed
]
As a drug or drug target
An artificially created biologic
immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Experiments in mice have demonstrated that OX40-Ig can reduce the symptoms associated with the cytokine storm (an immune overreaction) while allowing the immune system to fight off the virus successfully.[citation needed
]
An anti-OX40 antibody GSK3174998 has started clinical trials as a cancer treatment.TLR9 ligand activates expression of OX40 so that it can be affected.[5]
Interactions
CD134 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000186827 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "GSK and Merck to study immunotherapy combination as potential cancer treatment. Nov 2015". Archived from the original on 4 February 2017. Retrieved 6 April 2016.
- PMID 29386357.
- PMID 9488716.
- PMID 9418902.
External links
- Human TNFRSF4 genome location and TNFRSF4 gene details page in the UCSC Genome Browser.
Further reading
- So T, Salek-Ardakani S, Nakano H, Ware CF, Croft M (April 2004). "TNF receptor-associated factor 5 limits the induction of Th2 immune responses". Journal of Immunology. 172 (7): 4292–7. PMID 15034043.
- Song J, Salek-Ardakani S, Rogers PR, Cheng M, Van Parijs L, Croft M (February 2004). "The costimulation-regulated duration of PKB activation controls T cell longevity". Nature Immunology. 5 (2): 150–8. S2CID 10102422.
- Song J, So T, Cheng M, Tang X, Croft M (May 2005). "Sustained survivin expression from OX40 costimulatory signals drives T cell clonal expansion". Immunity. 22 (5): 621–31. PMID 15894279.
- Croft M (August 2003). "Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?". Nature Reviews. Immunology. 3 (8): 609–20. S2CID 10503208.
- Rogers PR, Song J, Gramaglia I, Killeen N, Croft M (September 2001). "OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells". Immunity. 15 (3): 445–55. PMID 11567634.
- Watts TH (2005). "TNF/TNFR family members in costimulation of T cell responses". Annual Review of Immunology. 23: 23–68. PMID 15771565.