The role of OX40 (CD134) in T-cell memory generation.
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.
Weinberg
Andrew D
AD
Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, 2N35, Portland, Oregon 97213, USA. andrew.weinberg@providence.org
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D053262:Receptors, OX40 / Q000819:agonists / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D053262:Receptors, OX40
Adv Exp Med Biol. 1991;292:167-76
1950767
J Immunol. 1999 Dec 15;163(12):6520-9
10586044
Annu Rev Immunol. 1998;16:201-23
9597129
J Neuroimmunol. 1994 Jan;49(1-2):161-70
8294553
J Immunol. 1986 May 1;136(9):3282-7
3082984
J Immunol. 2007 Oct 15;179(8):5014-23
17911586
Nat Immunol. 2003 Mar;4(3):225-34
12563257
J Immunol. 2003 Jan 1;170(1):99-106
12496388
Nat Rev Immunol. 2004 Jun;4(6):420-31
15173831
J Immunol. 2003 Dec 1;171(11):5997-6005
14634111
Semin Immunol. 1998 Dec;10(6):471-80
9826580
J Immunol. 2000 Sep 15;165(6):3043-50
10975814
Am J Surg. 2000 May;179(5):400-6
10930490
EMBO J. 1994 Sep 1;13(17):3992-4001
8076595
J Immunol. 1993 Nov 15;151(10):5261-71
8228223
J Immunol. 2005 Aug 1;175(3):1665-76
16034107
Trends Immunol. 2002 Feb;23(2):102-9
11929124
J Allergy Clin Immunol. 2004 Apr;113(4):683-9
15100674
J Immunol. 2008 Feb 15;180(4):2140-8
18250420
Nat Rev Cancer. 2007 Feb;7(2):95-106
17251916
Immunity. 2003 May;18(5):643-54
12753741
J Virol. 2004 Jun;78(11):5535-45
15140950
J Immunol. 2005 Sep 15;175(6):3534-41
16148096
J Immunol. 1999 Jun 15;162(12):7058-66
10358148
J Immunol. 2007 Aug 15;179(4):2195-202
17675479
J Exp Med. 1996 Mar 1;183(3):979-89
8642301
J Immunother. 2006 Nov-Dec;29(6):575-85
17063120
Mol Immunol. 1987 Dec;24(12):1281-90
2828930
J Neurosci Res. 1996 Jun 15;44(6):562-7
8794947
Int Immunol. 1998 Apr;10(4):453-61
9620601
Crit Rev Immunol. 2007;27(5):415-36
18197805
J Exp Med. 2003 Jul 21;198(2):315-24
12860930
Eur J Immunol. 2002 Nov;32(11):3326-35
12555678
Nature. 1992 Apr 16;356(6370):607-9
1313950
J Exp Med. 2000 Jan 17;191(2):365-74
10637280
J Immunol. 2004 Mar 15;172(6):3580-9
15004159
Immunity. 1999 Dec;11(6):699-708
10626892
Eur J Immunol. 2007 Jan;37(1):157-66
17183611
Nat Med. 1996 Feb;2(2):183-9
8574963
Eur J Immunol. 2004 Aug;34(8):2268-75
15259024
J Exp Med. 1994 Aug 1;180(2):757-62
7913952
J Immunol. 1998 Dec 15;161(12):6510-7
9862675
J Immunol. 2004 Sep 15;173(6):3716-24
15356117
J Immunol. 2007 Dec 1;179(11):7244-53
18025166
J Immunol. 1997 Oct 15;159(8):3838-48
9378971
J Immunol. 2006 May 15;176(10):5975-87
16670306
J Immunol. 2000 Feb 15;164(4):2160-9
10657670
Am J Surg. 1997 Sep;174(3):258-65
9324133
J Exp Med. 2007 May 14;204(5):1217-25
17485516
J Immunol. 2003 Jun 15;170(12):6125-32
12794142
Mol Cell Biol. 1991 Mar;11(3):1313-25
1996093
J Immunol. 2001 Dec 15;167(12):6804-11
11739496
J Immunol. 2001 Dec 1;167(11):6669-77
11714839
Immunity. 1995 May;2(5):507-21
7749983
J Immunol. 2002 Oct 15;169(8):4628-36
12370402
J Immunother. 2008 Apr;31(3):235-45
18317364
J Exp Med. 2001 Feb 5;193(3):387-92
11157058
Nat Rev Immunol. 2002 Apr;2(4):251-62
12001996
J Immunol. 2006 Jan 15;176(2):974-83
16393983
Immunity. 2001 Sep;15(3):445-55
11567634
Eur J Immunol. 1999 May;29(5):1610-6
10359115
J Exp Med. 1996 May 1;183(5):2185-95
8642328
J Immunol. 2000 Jan 1;164(1):107-12
10605000
Cancer Res. 2000 Oct 1;60(19):5514-21
11034096
J Immunol. 1999 Feb 1;162(3):1818-26
9973447