CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies.
Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8+T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8+T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8+T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8+T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.
Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, PA , USA.
Corinne J
CJ
Smith
Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, PA , USA.
Michael
M
Quinn
Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, PA , USA.
Christopher M
CM
Snyder
CMV-specific CD8 T cells; T cell localization; adoptive T cell therapy; effector T cells; memory T cells; tissue-resident memory cells
Am J Transplant. 2009 May;9(5):1214-22
19422346
J Exp Med. 2002 Jan 7;195(1):135-41
11781372
Mucosal Immunol. 2015 Sep;8(5):1060-71
25586557
Nat Immunol. 2013 Dec;14(12):1294-301
24162776
Lancet Infect Dis. 2004 Dec;4(12):725-38
15567122
Immunol Res. 2011 Dec;51(2-3):195-204
22058020
Clin Infect Dis. 2009 Dec 15;49(12):1851-60
19911966
J Infect. 2002 Feb;44(2):78-83
12076065
Immunity. 2003 May;18(5):593-603
12753737
Immunity. 2008 Dec 19;29(6):848-62
19100699
J Virol. 2012 Aug;86(15):8161-70
22623779
JAMA. 1989 Jun 23-30;261(24):3561-6
2542633
PLoS Pathog. 2011 Oct;7(10):e1002313
22046127
Immunity. 2013 Jan 24;38(1):187-97
23260195
Immunity. 2014 Oct 16;41(4):633-45
25308332
Transpl Immunol. 2010 May;23(1-2):86-91
20307665
J Leukoc Biol. 2014 Feb;95(2):215-24
24006506
J Virol. 2005 Sep;79(18):12112-6
16140789
Cell Rep. 2015 Nov 10;13(6):1125-36
26526997
J Gen Virol. 2011 Sep;92(Pt 9):1994-2005
21632567
Cell Rep. 2015 Nov 10;13(6):1137-48
26526996
Blood Cells Mol Dis. 2008 Jan-Feb;40(1):63-7
17869548
Cell. 2015 May 7;161(4):737-49
25957682
J Immunol. 2003 Feb 15;170(4):2022-9
12574372
J Immunol. 2006 Jul 1;177(1):450-8
16785542
Transpl Immunol. 2009 May;21(1):1-9
19162183
Antiviral Res. 2006 Sep;71(2-3):154-63
16765457
J Virol. 2002 Jan;76(1):151-64
11739681
J Immunol. 2015 Feb 15;194(4):1726-36
25595792
PLoS One. 2011 Jan 26;6(1):e16245
21298112
Eur J Immunol. 2005 Apr;35(4):1113-23
15756645
Blood. 2014 Jul 24;124(4):628-37
24855206
Blood. 2013 May 2;121(18):3745-58
23435462
Ir J Med Sci. 2009 Sep;178(3):333-6
19340518
Immunity. 2015 Dec 15;43(6):1101-11
26682984
J Immunol. 2014 Apr 1;192(7):2965-9
24591367
J Clin Invest. 2008 Jan;118(1):294-305
18060041
J Immunol. 2011 Oct 15;187(8):4068-76
21930973
Cell Rep. 2016 Feb 2;14 (4):760-71
26804910
J Virol. 2014 Aug;88(16):9010-6
24899187
J Exp Med. 2005 Sep 5;202(5):673-85
16147978
J Immunol. 2012 Sep 15;189(6):2702-6
22896631
J Clin Invest. 2010 Nov;120(11):4077-90
20921622
J Exp Med. 2010 Mar 15;207(3):553-64
20156972
Nature. 2012 Nov 15;491(7424):463-7
23075848
Herpesviridae. 2011 Mar 15;2(1):5
21429183
Blood. 2007 Dec 15;110(13):4360-6
17878400
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8623-8
19433785
Science. 2014 Oct 3;346(6205):101-5
25278612
J Immunol. 2012 Oct 1;189(7):3462-71
22922816
Nat Protoc. 2014 Jan;9(1):209-22
24385150
Blood. 2010 Nov 18;116(20):4360-7
20625005
Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16741-6
21930933
Clin Infect Dis. 2006 Nov 1;43(9):1143-51
17029132
World J Transplant. 2015 Dec 24;5(4):287-91
26722656
Nat Immunol. 2013 Dec;14(12):1285-93
24162775
Nat Immunol. 2009 May;10(5):524-30
19305395
Immunity. 2004 May;20(5):551-62
15142524
Nature. 2012 Feb 29;483(7388):227-31
22388819
Clin Infect Dis. 2013 Mar;56(6):817-24
23196955
Lancet. 2003 Oct 25;362(9393):1375-7
14585640
Curr Infect Dis Rep. 2012 Aug;14(4):435-44
22688820
PLoS One. 2011 Feb 03;6(2):e14646
21304910
J Clin Invest. 2011 Jun;121(6):2254-63
21537083
Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17872-9
20923878
Immunity. 2014 May 15;40(5):747-57
24792910
Blood. 1994 Apr 1;83(7):1971-9
8142663
Nat Rev Immunol. 2012 Nov;12(11):749-61
23080391
J Virol. 2000 Dec;74(24):11495-503
11090146
J Exp Med. 2005 Aug 1;202(3):379-86
16061727
Blood. 2005 Sep 15;106(6):2091-8
15947093
Science. 1992 Jul 10;257(5067):238-41
1352912
Clin Exp Immunol. 2003 Oct;134(1):9-12
12974748
Nat Rev Immunol. 2003 Nov;3(11):867-78
14668803
Science. 2016 Apr 22;352(6284):459-63
27102484
J Virol. 2000 Aug;74(16):7496-507
10906203
J Immunol. 2006 Feb 15;176(4):2079-83
16455963
Immunity. 2006 Sep;25(3):511-20
16973385
Eur J Immunol. 2015 Oct;45(10):2945-58
26179882
Immunity. 2007 Oct;27(4):670-84
17950003
J Exp Med. 2013 Aug 26;210(9):1855-69
23960189
Biol Blood Marrow Transplant. 2007 Jul;13(7):765-70
17580254
Clin Infect Dis. 2011 Jan 1;52(1):49-57
21148519
Science. 2014 Oct 3;346(6205):93-8
25170048
Immunity. 2008 Oct 17;29(4):650-9
18957267
J Immunol. 2011 Dec 1;187(11):5510-4
22058417
Proc Natl Acad Sci U S A. 2012 May 1;109(18):7037-42
22509047
Nature. 1999 Oct 14;401(6754):708-12
10537110
J Transl Med. 2014 Dec 16;12:336
25510656
Ann N Y Acad Sci. 1991 Dec 30;636:184-95
1665321
Nat Immunol. 2013 May;14(5):509-13
23542740
J Med Virol. 2013 May;85(5):893-8
23508914
Blood. 2009 Dec 3;114(24):5071-80
19776383
PLoS Pathog. 2014 Jul 03;10(7):e1004233
24992722
J Immunol. 2007 Dec 1;179(11):7220-4
18025163
Immunity. 2010 Jul 23;33(1):128-40
20619696
Immunology. 2011 Jan;132(1):27-38
20738423
J Immunol. 2012 May 15;188(10):4866-75
22504644
Science. 2014 Oct 3;346(6205):98-101
25170049
Clin Transl Immunology. 2015 Mar 27;4(3):e35
25859390
Rev Med Virol. 2016 May;26(3):161-82
26990717
Nat Immunol. 2014 Dec;15(12):1104-15
25396352
J Immunol. 2006 Jul 15;177(2):831-9
16818737
Med Microbiol Immunol. 2012 Nov;201(4):551-66
22991040
Blood. 2002 Jun 1;99(11):3916-22
12010789
Immunol Cell Biol. 2013 Mar;91(3):240-9
23295361
Science. 2001 Mar 23;291(5512):2413-7
11264538
Nat Rev Immunol. 2016 Feb;16(2):79-89
26688350
J Clin Invest. 2005 Dec;115(12):3473-83
16308575
Am J Transplant. 2002 Oct;2(9):850-6
12392291
Am J Transplant. 2015 Mar;15(3):827-32
25648555
N Engl J Med. 1995 Oct 19;333(16):1038-44
7675046
Science. 2015 Jun 5;348(6239):aaa0698
26045439
PLoS One. 2014 Mar 11;9(3):e91054
24618819
Clin Microbiol Rev. 2009 Jan;22(1):76-98, Table of Contents
19136435