The Role of OX40 (CD134) in T-cell Memory Generation

Overview

Journal Adv Exp Med Biol

Specialties Biology
General Medicine

Date 2010 Aug 28

PMID 20795540

Citations 7

Authors

Andrew D Weinberg

Affiliations

Soon will be listed here.

Abstract

Memory T-cell generation is limited by activation-induced cell death during the effector T-cell stage. Cell surface proteins are known to transmit signals that either accentuate or limit T-cell death after activation. This chapter will focus on the TNF-receptor family member OX40, which is expressed on effector T cells and when engaged greatly enhances survival of T cells leading to increased memory T-cell generation. Targeting OX40 in vivo can alter the fate ofT-cell survival. Enhancing OX40 signaling during Ag priming through agonists increases memory T-cell development, while blocking OX40 signaling decreases the memory T-cell pool. These two opposing outcomes provide therapeutic tools for blocking inflammation in autoimmune conditions and enhancing immunity in hosts harboring cancer or chronic pathogens. OX40 agonists and antagonists are in the first stages of human clinical trials and their therapeutic potential will soon be realized.

Citing Articles

Comparison of OX40 expression in patients with multiple sclerosis and neuromyelitis optica as an approach to diagnosis.

Manian M, Motallebnezhad M, Nedaeinia R, Salehi R, Khani L, Ferns G Allergy Asthma Clin Immunol. 2023; 19(1):19.

PMID: 36899405 PMC: 10007837. DOI: 10.1186/s13223-023-00772-9.

A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers.

Diab A, Hamid O, Thompson J, Ros W, Eskens F, Doi T Clin Cancer Res. 2021; 28(1):71-83.

PMID: 34615725 PMC: 9401502. DOI: 10.1158/1078-0432.CCR-21-0845.

Transplant research in nonhuman primates to evaluate clinically relevant immune strategies in organ transplantation.

Fitch Z, Schmitz R, Kwun J, Hering B, Madsen J, Knechtle S Transplant Rev (Orlando). 2019; 33(3):115-129.

PMID: 31027947 PMC: 6599548. DOI: 10.1016/j.trre.2019.03.002.

TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury.

Lan P, Fan Y, Zhao Y, Lou X, Monsour H, Zhang X J Clin Invest. 2017; 127(6):2222-2234.

PMID: 28436935 PMC: 5451219. DOI: 10.1172/JCI91075.

Interruption of OX40L signaling prevents costimulation blockade-resistant allograft rejection.

Kitchens W, Dong Y, Mathews D, Breeden C, Strobert E, Fuentes M JCI Insight. 2017; 2(5):e90317.

PMID: 28289708 PMC: 5333968. DOI: 10.1172/jci.insight.90317.

References

Jenkins M, Mueller D, Schwartz R, Carding S, Bottomley K, Stadecker M . Induction and maintenance of anergy in mature T cells. Adv Exp Med Biol. 1991; 292:167-76. DOI: 10.1007/978-1-4684-5943-2_19. View

Pippig S, Pena-Rossi C, Long J, Godfrey W, Fowell D, Reiner S . Robust B cell immunity but impaired T cell proliferation in the absence of CD134 (OX40). J Immunol. 1999; 163(12):6520-9. View

Dutton R, Bradley L, Swain S . T cell memory. Annu Rev Immunol. 1998; 16:201-23. DOI: 10.1146/annurev.immunol.16.1.201. View

Weinberg A, Celnik B, Vainiene M, Buenafe A, Vandenbark A, Offner H . The effect of TCR V beta 8 peptide protection and therapy on T cell populations isolated from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. J Neuroimmunol. 1994; 49(1-2):161-70. DOI: 10.1016/0165-5728(94)90192-9. View

Martin P, Ledbetter J, Morishita Y, June C, Beatty P, Hansen J . A 44 kilodalton cell surface homodimer regulates interleukin 2 production by activated human T lymphocytes. J Immunol. 1986; 136(9):3282-7. View

Soroosh P, Ine S, Sugamura K, Ishii N . Differential requirements for OX40 signals on generation of effector and central memory CD4+ T cells. J Immunol. 2007; 179(8):5014-23. DOI: 10.4049/jimmunol.179.8.5014. View

Wherry E, Teichgraber V, Becker T, Masopust D, Kaech S, Antia R . Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003; 4(3):225-34. DOI: 10.1038/ni889. View

Gri G, Gallo E, Di Carlo E, Musiani P, Colombo M . OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response. J Immunol. 2002; 170(1):99-106. DOI: 10.4049/jimmunol.170.1.99. View

Sugamura K, Ishii N, Weinberg A . Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40. Nat Rev Immunol. 2004; 4(6):420-31. DOI: 10.1038/nri1371. View

10.

Prell R, Evans D, Thalhofer C, Shi T, Funatake C, Weinberg A . OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent. J Immunol. 2003; 171(11):5997-6005. DOI: 10.4049/jimmunol.171.11.5997. View

11.

Weinberg A, Vella A, Croft M . OX-40: life beyond the effector T cell stage. Semin Immunol. 1998; 10(6):471-80. DOI: 10.1006/smim.1998.0146. View

12.

Gramaglia I, Jember A, Pippig S, Weinberg A, Killeen N, Croft M . The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion. J Immunol. 2000; 165(6):3043-50. DOI: 10.4049/jimmunol.165.6.3043. View

13.

Ramstad T, Lawnicki L, Vetto J, Weinberg A . Immunohistochemical analysis of primary breast tumors and tumor-draining lymph nodes by means of the T-cell costimulatory molecule OX-40. Am J Surg. 2000; 179(5):400-6. DOI: 10.1016/s0002-9610(00)00361-5. View

14.

Baum P, Gayle 3rd R, Ramsdell F, Srinivasan S, Sorensen R, Watson M . Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. EMBO J. 1994; 13(17):3992-4001. PMC: 395319. DOI: 10.1002/j.1460-2075.1994.tb06715.x. View

15.

Calderhead D, Buhlmann J, van den Eertwegh A, Claassen E, Noelle R, Fell H . Cloning of mouse Ox40: a T cell activation marker that may mediate T-B cell interactions. J Immunol. 1993; 151(10):5261-71. View

16.

Hendriks J, Xiao Y, Rossen J, van der Sluijs K, Sugamura K, Ishii N . During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion. J Immunol. 2005; 175(3):1665-76. DOI: 10.4049/jimmunol.175.3.1665. View

17.

Weinberg A . OX40: targeted immunotherapy--implications for tempering autoimmunity and enhancing vaccines. Trends Immunol. 2002; 23(2):102-9. DOI: 10.1016/s1471-4906(01)02127-5. View

18.

Burgess J, Carlin S, Pack R, Arndt G, Au W, Johnson P . Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma?. J Allergy Clin Immunol. 2004; 113(4):683-9. DOI: 10.1016/j.jaci.2003.12.311. View

19.

Ruby C, Montler R, Zheng R, Shu S, Weinberg A . IL-12 is required for anti-OX40-mediated CD4 T cell survival. J Immunol. 2008; 180(4):2140-8. DOI: 10.4049/jimmunol.180.4.2140. View

20.

Melero I, Hervas-Stubbs S, Glennie M, Pardoll D, Chen L . Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007; 7(2):95-106. DOI: 10.1038/nrc2051. View