Repertoire development and the control of cytotoxic/effector function in human gammadelta T cells.
T cells develop into two major populations distinguished by their T cell receptor (TCR) chains. Cells with the alphabeta TCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate gammadelta TCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vgamma2Vdelta2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature on gammadelta T cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen-reactive Vgamma2Vdelta2 cells. A unique mechanism for MHC-independent repertoire selection is linked to the control of effector function that is vital to the role for gammadelta T cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.
Urban
Elizabeth M
EM
Institute of Human Virology, University of Maryland, School of Medicine, 725 W Lombard Street, Baltimore, MD 21201, USA.
Chapoval
Andrei I
AI
Pauza
C David
CD
D000818:Animals; D019002:CD56 Antigen / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007157:Immunologic Surveillance; D007167:Immunotherapy; D038041:Lymphopoiesis; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D019002:CD56 Antigen; D006680:HLA Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta
Chem Rev. 1972 Apr;72(2):115-55
4552138
Scand J Immunol. 2007 Aug-Sep;66(2-3):320-8
17635809
Adv Immunol. 2006;90:1-50
16730260
Annu Rev Immunol. 2002;20:217-51
11861603
J Immunol. 1999 May 1;162(9):5033-6
10227967
Eur J Immunol. 1997 Nov;27(11):2812-21
9394804
EMBO J. 1994 Oct 3;13(19):4482-9
7925290
J Immunol. 2008 Oct 1;181(7):4798-806
18802083
Nat Immunol. 2007 Feb;8(2):137-44
17242687
Cancer Immunol Immunother. 2008 Apr;57(4):531-9
17764010
Eur J Immunol. 1993 Apr;23(4):804-8
8384559
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8175-9
8058775
J Infect Dis. 1990 May;161(5):1013-6
2324529
J Exp Med. 2003 Jan 20;197(2):163-8
12538656
J Natl Cancer Inst. 1991 Nov 6;83(21):1564-9
1683671
J Immunol. 2005 Oct 15;175(8):5481-8
16210656
Microbes Infect. 1999 Mar;1(3):175-86
10594981
Immunity. 2005 Jan;22(1):71-80
15664160
Cancer Immunol Immunother. 2007 Jun;56(6):819-29
17131122
FEBS Lett. 2003 Jun 5;544(1-3):4-10
12782281
BMC Immunol. 2009 Sep 21;10:50
19772585
Nature. 1986 Jul 10-16;322(6075):179-81
3487737
Science. 2005 Apr 8;308(5719):227-31
15821084
Science. 2005 Apr 8;308(5719):252-5
15821090
Nature. 1986 Jul 10-16;322(6075):145-9
3755221
J Exp Med. 1991 Jun 1;173(6):1311-22
1827824
Eur J Immunol. 2005 Jun;35(6):1896-905
15864777
J Immunol. 2008 Feb 1;180(3):1979-90
18209097
Biochem J. 1993 Oct 15;295 ( Pt 2):517-24
8240251
J Exp Med. 1986 Jul 1;164(1):351-6
3088199
J Immunol. 1993 Aug 1;151(3):1214-23
8393042
Cell Mol Life Sci. 2006 Sep;63(18):2089-94
17003966
J Immunol. 1991 Jun 15;146(12):4421-6
1710251
Infect Immun. 1992 Mar;60(3):1229-31
1531813
Blood. 2000 Jul 15;96(2):384-92
10887096
J Exp Med. 1994 Aug 1;180(2):569-76
7519241
Immunol Rev. 2007 Feb;215:46-58
17291278
Eur J Immunol. 1997 Dec;27(12):3368-79
9464825
Adv Cancer Res. 1973;18:211-30
4148723
Immunol Rev. 1988 Aug;104:81-120
3049319
Science. 1987 May 15;236(4803):799-806
3576199
J Exp Med. 1989 Jun 1;169(6):2233-8
2471777
J Natl Cancer Inst. 1994 Nov 16;86(22):1711-6
7966400
J Immunol. 1997 Dec 15;159(12):6009-17
9550399
Immunol Today. 1997 Jun;18(6):267-8
9190110
Nat Med. 2003 Mar;9(3):269-77
12612576
J Infect Dis. 1992 Mar;165(3):506-12
1538155
J Exp Med. 1990 May 1;171(5):1597-612
2185330
J Immunol. 2005 Aug 15;175(4):2144-51
16081780
J Immunol. 2001 Dec 15;167(12):6773-9
11739492
FEBS Lett. 2001 Dec 7;509(2):317-22
11741609
PLoS One. 2009 Nov 04;4(11):e7726
19888466
Nat Rev Immunol. 2002 May;2(5):336-45
12033739
AIDS Res Hum Retroviruses. 2003 Jan 1;19(1):21-9
12581513
Immunology. 2001 Sep;104(1):19-27
11576216
Cancer Immunol Immunother. 2007 Aug;56(8):1285-97
17265022
Nat Immunol. 2003 Oct;4(10):991-8
14502287
N Engl J Med. 1999 Mar 4;340(9):737-8
10068336
Blood. 1999 May 1;93(9):3033-43
10216100
Microbes Infect. 1999 Mar;1(3):203-12
10801231
Anticancer Res. 2008 Mar-Apr;28(2B):1263-9
18505064
Int J Cancer. 2008 Jun 1;122(11):2526-34
18307255
J Immunol. 1999 Mar 1;162(5):2575-80
10072498
Immunol Lett. 1990 Aug;25(1-3):139-41
2149360
Nat Rev Immunol. 2006 May;6(5):383-93
16622476
Immunol Rev. 2001 Jun;181:185-92
11513139
Cancer Immunol Immunother. 2009 Jan;58(1):31-8
18458903
J Exp Med. 1989 Nov 1;170(5):1521-35
2572670
J Immunol. 1995 Feb 1;154(3):998-1006
7529807
J Immunol. 2004 Dec 1;173(11):6767-76
15557170
J Immunol. 2000 Sep 1;165(5):2643-50
10946293
Immunity. 2004 Aug;21(2):137-48
15308095
Immunol Today. 2000 Apr;21(4):187-91
10740240
Science. 1999 Jul 30;285(5428):727-9
10426993
Leuk Lymphoma. 2005 May;46(5):671-80
16019504
Microbes Infect. 2005 Mar;7(3):503-9
15823511
Curr Top Microbiol Immunol. 1991;173:183-8
1833141
Curr Opin Immunol. 2006 Apr;18(2):135-42
16480861
Breast Cancer Res Treat. 2005 Sep;93(2):169-75
16187237
Genes Dev. 1991 Aug;5(8):1357-66
1869046
J Immunol. 2006 Feb 1;176(3):1543-52
16424183
J Med Primatol. 2000 Dec;29(6):387-96
11168829
J Immunol. 1993 May 15;150(10):4244-52
8387091
J Immunol. 1991 Nov 15;147(10):3360-9
1658147
Nat Immunol. 2006 Aug;7(8):843-50
16829962
Immunity. 2001 Jul;15(1):83-93
11485740
Infect Immun. 1993 Jan;61(1):197-203
8418042
Science. 2005 Feb 11;307(5711):925-8
15591166
Clin Cancer Res. 2008 Jul 1;14(13):4232-40
18594005
Immunity. 1995 Oct;3(4):495-507
7584140
J Immunol. 2004 May 1;172(9):5544-52
15100297
Clin Immunol. 2009 Jun;131(3):367-73
19250873
Immunity. 2006 Jan;24(1):53-64
16413923
FEMS Immunol Med Microbiol. 1999 Sep;25(4):371-8
10497868
Immunity. 1997 Jan;6(1):1-11
9052832
Proc Natl Acad Sci U S A. 1982 Jul;79(13):4234-8
7051008
J Immunol. 1990 Nov 15;145(10):3202-8
2146317
J Exp Med. 1990 May 1;171(5):1567-79
2185329
J Exp Med. 1989 Nov 1;170(5):1757-61
2478655
Blood. 2003 Jul 1;102(1):200-6
12623838
AIDS. 2009 Sep 24;23(15):1955-64
19609200
Cancer Res. 2007 Aug 1;67(15):7450-7
17671215
Int Immunol. 2003 Nov;15(11):1301-7
14565928
Science. 1990 Nov 30;250(4985):1269-73
1978758
Nat Rev Immunol. 2007 Jul;7(7):505-18
17589542
J Immunol. 2005 Feb 1;174(3):1338-47
15661891
Science. 2005 Jul 8;309(5732):264-8
15933162
Int Arch Allergy Immunol. 2000 May;122(1):1-7
10859464
Eur J Immunol. 1990 May;20(5):1175-9
2141570
J Immunol. 2001 May 1;166(9):5508-14
11313389
Nature. 2001 Jun 14;411(6839):820-4
11459064
J Immunol. 2003 Apr 1;170(7):3608-13
12646624
Immunity. 1997 Jul;7(1):83-95
9252122
J Immunol. 2001 Nov 1;167(9):5092-8
11673519
Nat Immunol. 2009 Apr;10(4):427-36
19270712
Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10600-5
9380681
J Immunol. 2008 Dec 1;181(11):7738-50
19017963
J Immunol. 2006 Nov 1;177(9):6129-36
17056540
J Immunol. 2000 Feb 1;164(3):1148-52
10640724
Nature. 1995 May 11;375(6527):155-8
7753173
Hepatology. 2001 May;33(5):1312-20
11343261
Immunity. 1999 Jul;11(1):57-65
10435579
J Immunol. 2004 Feb 1;172(3):1637-45
14734745
AIDS. 2008 Oct 18;22(16):2143-53
18832878
Nature. 2006 Dec 21;444(7122):1073-7
17190001
Immunity. 2008 Jul 18;29(1):90-100
18585064
Annu Rev Immunol. 2000;18:975-1026
10837080
J Immunol. 2007 Apr 15;178(8):4947-55
17404276
Nat Genet. 2008 May;40(5):656-62
18408721
Eur J Immunol. 1994 Dec;24(12):3044-9
7805732
Trends Immunol. 2008 Jun;29(6):251-5
18472300
Nature. 1987 Sep 24-30;329(6137):336-9
3114648
Blood. 2003 Sep 15;102(6):2310-1
12959943
Science. 2000 Jan 14;287(5451):314-6
10634788