Hematopoietic progenitor migration to the adult thymus.
Although most hematopoietic lineages develop in the bone marrow (BM), T cells uniquely complete their development in the specialized environment of the thymus. Hematopoietic stem cells with long-term self-renewal capacity are not present in the thymus. As a result, continuous T cell development requires that BM-derived progenitors be imported into the thymus throughout adult life. The process of thymic homing begins with the mobilization of progenitors out of the BM, continues with their circulation in the bloodstream, and concludes with their settling in the thymus. This review will discuss each of these steps as they occur in the unirradiated and postirradiation scenarios, focusing on the molecular mechanisms of regulation. Improved knowledge about these early steps in T cell generation may accelerate the development of new therapeutic options in patients with impaired T cell number or function.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Daniel A
DA
Zlotoff
Avinash
A
Bhandoola
D000328:Adult; D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D016922:Cellular Senescence / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*
Nature. 2008 Apr 10;452(7188):764-7
18401411
J Immunol. 1990 Dec 1;145(11):3661-8
2123223
Blood. 2003 Jul 15;102(2):421-8
12663447
Blood. 2010 Feb 11;115(6):1137-44
20009033
Genes Dev. 2009 Oct 15;23(20):2376-81
19833765
J Clin Invest. 2003 Oct;112(7):1095-107
14523046
Nat Rev Immunol. 2003 Nov;3(11):867-78
14668803
Blood. 2001 Mar 15;97(6):1534-42
11238087
Semin Immunopathol. 2008 Dec;30(4):457-77
18982327
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7455-60
11390986
Nat Med. 2004 Aug;10(8):858-64
15235597
Blood. 2001 Jun 1;97(11):3354-60
11369624
J Immunol. 1996 Jun 15;156(12):4609-16
8648103
Science. 1988 Jul 1;241(4861):58-62
2898810
Blood. 2008 Jun 15;111(12):5562-70
18424665
Blood. 2003 Nov 1;102(9):3427-38
12869514
Immunol Rev. 1997 Jun;157:13-40
9255619
J Exp Med. 2006 Mar 20;203(3):675-87
16505143
J Exp Med. 2010 May 10;207(5):1113-24
20404103
Blood. 2000 May 15;95(10):3025-31
10807765
Exp Hematol. 2003 Oct;31(10):953-8
14550811
Blood. 2009 Jan 22;113(4):807-15
18927436
Nat Immunol. 2005 Jul;6(7):663-70
15951813
Blood. 2000 Sep 15;96(6):2299-303
10979980
J Immunol. 2005 Nov 1;175(9):5848-56
16237077
Eur J Immunol. 2005 Jul;35(7):2019-30
15971276
Nat Immunol. 2003 Sep;4(9):866-73
12925850
Exp Hematol. 1979 Oct;7(9):483-9
527693
Semin Immunol. 2005 Oct;17(5):370-7
15964201
EMBO J. 1994 Sep 15;13(18):4229-40
7523109
Curr Opin Organ Transplant. 2008 Feb;13(1):53-8
18660707
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2788-92
1672767
Best Pract Res Clin Haematol. 2008 Sep;21(3):503-19
18790452
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7006-11
16641096
Immunity. 2001 Oct;15(4):659-69
11672547
J Clin Invest. 2003 Jan;111(2):187-96
12531874
Cell. 2005 Apr 22;121(2):295-306
15851035
J Exp Med. 2002 Apr 1;195(7):919-29
11927635
Blood. 1962 Jun;19:702-14
13900318
Immunity. 2003 Aug;19(2):257-67
12932359
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1469-74
16432201
Transplantation. 1975 Jan;19(1):2-11
1118887
Clin Cancer Res. 2009 Aug 1;15(15):4944-53
19602548
Blood. 1997 Jul 15;90(2):850-7
9226186
Nat Rev Immunol. 2008 May;8(5):362-71
18379575
PLoS Biol. 2004 Mar;2(3):E75
15024423
Blood. 2006 Mar 15;107(6):2453-60
16304055
Exp Hematol. 2002 Sep;30(9):973-81
12225788
Blood. 1998 Apr 15;91(8):2672-8
9531575
Eur J Immunol. 2006 Jan;36(1):73-81
16342233
Blood. 2007 Aug 15;110(4):1161-7
17456721
Science. 2009 Jul 10;325(5937):217-8
19590005
Blood. 2002 Jun 15;99(12):4307-17
12036856
Nat Immunol. 2010 Jul;11(7):585-93
20543838
Blood. 2006 Sep 15;108(6):1797-808
16741253
Nat Immunol. 2005 Jun;6(6):626-34
15880112
J Immunol. 2006 Sep 1;177(5):2880-7
16920923
Cell. 1997 Nov 28;91(5):661-72
9393859
Blood. 2005 Jan 1;105(1):31-9
15358618
Stem Cells Dev. 2005 Apr;14(2):199-203
15910246
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6228-33
11983913
Immunity. 2002 Dec;17(6):749-56
12479821
Blood. 1996 May 1;87(9):3984-92
8611731
Blood. 2006 May 1;107(9):3511-9
16397133
J Immunol. 2008 Dec 1;181(11):7514-24
19017941
Science. 1996 Jul 12;273(5272):242-5
8662508
Blood. 1998 Dec 1;92(11):4464-71
9834254
J Exp Med. 1976 May 1;143(5):1082-99
4575
J Immunol. 2009 Dec 15;183(12):7768-77
20007571
Immunity. 2004 Sep;21(3):315-29
15357943
Immunol Rev. 2006 Feb;209:47-57
16448533
Curr Opin Hematol. 2002 May;9(3):183-9
11953662
Bone Marrow Transplant. 2005 May;35(10):935-42
15806121
Transplantation. 2003 Jun 27;75(12):1977-83
12829897
Nat Immunol. 2004 Mar;5(3):247-53
14985712
Immunol Rev. 1986 Jun;91:129-57
3525392
Nature. 2008 Apr 10;452(7188):768-72
18401412
J Exp Med. 2005 Apr 18;201(8):1307-18
15837815
Blood. 2010 Mar 11;115(10):1897-905
19965655
Blood. 2006 Oct 15;108(8):2531-9
16809609
Blood. 2005 Mar 1;105(5):1930-6
15522952
Science. 2002 Sep 27;297(5590):2256-9
12215650
Science. 2001 Nov 30;294(5548):1933-6
11729320
Semin Immunopathol. 2008 Dec;30(4):439-56
18974988
Blood. 2010 Mar 11;115(10):1906-12
20040757
Cell Mol Immunol. 2006 Feb;3(1):11-9
16549044
Immunity. 2002 Aug;17(2):117-30
12196284
Blood Cells Mol Dis. 2008 Jan-Feb;40(1):44-7
17905611
J Clin Invest. 2002 Oct;110(8):1165-74
12393852
N Engl J Med. 1995 Jan 19;332(3):143-9
7800006
Nature. 1963 Feb 2;197:452-4
13970094
Ann N Y Acad Sci. 2010 Mar;1192:12-8
20392212
J Exp Med. 1991 Dec 1;174(6):1617-27
1683894
Nature. 1998 Jun 11;393(6685):595-9
9634238
Semin Immunol. 1997 Dec;9(6):339-46
9405262
J Clin Invest. 2000 Dec;106(11):1331-9
11104786
J Exp Med. 2006 Aug 7;203(8):1977-84
16847069
Clin Cancer Res. 2008 Feb 15;14(4):1138-49
18281548
J Immunol. 2007 Apr 1;178(7):4147-52
17371970
Nat Immunol. 2003 Feb;4(2):168-74
12514733
Eur J Immunol. 2007 Mar;37(3):830-7
17295389
J Immunol. 1994 May 1;152(9):4320-7
8157955
Immunity. 2007 Jan;26(1):105-16
17222572
Blood. 2001 Sep 1;98(5):1601-6
11520813
Bone Marrow Transplant. 2008 Jan;41(1):55-62
17934532
J Immunol. 2007 Feb 15;178(4):2008-17
17277104
Nature. 1996 Aug 15;382(6592):635-8
8757135
J Immunol. 1987 Jun 1;138(11):3598-603
3108369
Annu Rev Immunol. 2005;23:945-74
15771590
Immunol Cell Biol. 2008 Oct;86(7):552-3
18663375
J Immunol. 2002 Mar 15;168(6):2811-9
11884450
Exp Hematol. 2002 May;30(5):440-9
12031650
J Exp Med. 2009 Apr 13;206(4):761-78
19289576
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6311-6
17404232
Cell Stem Cell. 2009 Jan 9;4(1):62-72
19128793
Blood. 2007 Aug 1;110(3):860-9
17416737
Blood. 1999 Jan 15;93(2):467-80
9885208
Eur J Immunol. 2010 Mar;40(3):688-98
20039302
Clin Immunol. 2004 Dec;113(3):285-98
15507394
Nat Rev Immunol. 2008 Apr;8(4):290-301
18323850
Blood. 1982 Apr;59(4):844-50
6460536
J Exp Med. 2004 Aug 16;200(4):481-91
15302903
Semin Immunol. 2005 Oct;17(5):337-46
15961315
Nature. 2008 Mar 27;452(7186):442-7
18256599
J Immunol. 1992 Mar 15;148(6):1604-12
1347301
Annu Rev Immunol. 1996;14:29-47
8717506
Semin Immunopathol. 2008 Dec;30(4):425-37
18949477
Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18333-8
19815516
J Immunol. 2007 Mar 15;178(6):3551-7
17339451
Semin Immunol. 2007 Oct;19(5):318-30
18023361
J Clin Invest. 2005 Apr;115(4):930-9
15776111
J Immunol. 2007 Jun 1;178(11):7473-84
17513799
Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11995-2000
19587240
Nat Immunol. 2005 Jul;6(7):671-9
15951812
J Exp Med. 1986 Jan 1;163(1):1-17
3510267
Immunity. 2007 Jun;26(6):678-89
17582341
Blood. 1995 Apr 15;85(8):2269-75
7718900
Nat Med. 2006 Sep;12(9):1039-47
16936725
J Immunol. 2005 Aug 15;175(4):2741-53
16081852
Blood. 2008 Feb 1;111(3):1318-26
17959857
Blood. 2001 Sep 1;98(5):1289-97
11520773
Blood. 2010 Apr 1;115(13):2601-9
19996414
Nat Immunol. 2002 Jul;3(7):687-94
12068293
Immunol Rev. 1997 Jun;157:73-8
9255623
Nat Immunol. 2004 Sep;5(9):953-60
15300246
Transplantation. 2005 Dec 15;80(11):1604-13
16371932
J Exp Med. 2008 Mar 17;205(3):523-31
18299401
Cell. 2009 Jul 10;138(1):186-97
19559469
Lancet. 2000 May 27;355(9218):1875-81
10866444
Trends Immunol. 2006 Oct;27(10):477-84
16920024
Blood. 2004 Jan 1;103(1):110-9
12958067
Immunol Res. 2009;44(1-3):160-8
19340403
J Immunol. 2005 Aug 15;175(4):2321-30
16081802