Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation.
Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions.
Division of Hematology, Department of Medical Specialties, Faculty of Medicine, Geneva University Hospitals, University of Geneva , Geneva , Switzerland.
Stavroula
S
Masouridi-Levrat
Division of Hematology, Department of Medical Specialties, Faculty of Medicine, Geneva University Hospitals, University of Geneva , Geneva , Switzerland.
Federico
F
Simonetta
Division of Hematology, Department of Medical Specialties, Faculty of Medicine, Geneva University Hospitals, University of Geneva , Geneva , Switzerland.
Yves
Y
Chalandon
HSCT; bone marrow failure; graft failure; poor graft function
Int Immunol. 1998 Jun;10(6):785-90
9678759
Transplantation. 1987 Jun;43(6):842-7
3296349
Bone Marrow Transplant. 2009 Mar;43(6):447-54
18955980
J Exp Med. 2001 Oct 1;194(7):941-52
11581316
Blood. 2004 Sep 15;104(6):1671-8
15166031
Blood. 1995 Jun 1;85(11):3183-90
7538820
Nature. 2011 Jun 08;474(7350):216-9
21654805
Lancet. 1990 Jan 20;335(8682):131-4
1967432
Ann Hematol. 2003 Jul;82(7):410-5
12750845
PLoS One. 2016 Jan 05;11(1):e0146245
26731275
Front Immunol. 2016 Mar 30;7:118
27066008
Transplantation. 2011 Aug 15;92(3):280-8
21697774
J Hematol Oncol. 2016 May 18;9(1):46
27193054
Blood. 2012 Jan 5;119(1):296-307
22010102
Immunity. 1999 Nov;11(5):579-90
10591183
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5460-5
16567639
Biol Blood Marrow Transplant. 2000;6(6):604-12
11128810
Blood. 2008 Sep 1;112(5):2111-9
18552211
Biol Blood Marrow Transplant. 2005 May;11(5):389-98
15846293
Nat Med. 2008 Jan;14(1):88-92
18066074
Blood. 2005 Feb 15;105(4):1828-36
15494429
J Immunol. 2009 Jun 15;182(12):7364-9
19494258
Biol Blood Marrow Transplant. 2013 Jun;19(6):876-87
23523972
J Exp Med. 2011 Aug 1;208(8):1563-70
21768269
Transplantation. 2006 Jul 27;82(2):218-26
16858285
Exp Hematol. 1999 May;27(5):895-903
10340406
J Immunol. 2008 Jan 1;180(1):49-57
18097003
Blood. 1992 Aug 1;80(3):670-7
1379086
Bone Marrow Transplant. 2013 Apr;48(4):537-43
23222384
Blood. 2010 Jul 1;115(26):5401-11
20354171
Blood. 1992 Nov 1;80(9):2406-11
1421412
J Cell Physiol. 1995 Dec;165(3):538-46
7593233
Blood. 1986 Oct;68(4):861-8
3530349
Blood. 2014 May 1;123(18):2882-92
24591203
Eur J Immunol. 1977 Sep;7(9):655-63
336380
Blood. 2007 Oct 1;110(7):2764-7
17638847
J Exp Med. 1994 Sep 1;180(3):1177-82
7520470
Blood. 2000 Feb 1;95(3):1100-5
10648428
Biol Blood Marrow Transplant. 2016 Aug;22(8):1376-82
27131864
Blood. 1995 Oct 15;86(8):2930-7
7579385
Nature. 2012 Jan 11;481(7382):506-10
22237025
Biol Blood Marrow Transplant. 2014 Apr;20(4):495-500
24374213
Biol Blood Marrow Transplant. 2009 Jul;15(7):785-94
19539209
Haematologica. 2011 Dec;96(12 ):1838-45
21880629
Transplantation. 2009 Oct 27;88(8):1019-24
19855248
Blood. 2000 Nov 1;96(9):3126-32
11049993
Transplantation. 1990 Feb;49(2):453-8
2305471
Blood. 1997 May 15;89(10):3565-73
9160661
Blood. 2001 Sep 15;98(6):1782-91
11535512
Blood. 2010 Apr 1;115(13):2704-8
20089963
Leukemia. 2015 Aug;29(8):1754-62
25772027
Biol Blood Marrow Transplant. 2005 Aug;11(8):576-86
16041307
Bone Marrow Transplant. 2015 Sep;50(9):1187-94
26030050
Blood. 1998 Jul 1;92(1):101-7
9639505
J Exp Med. 1993 Aug 1;178(2):703-12
8101864
Bone Marrow Transplant. 2012 Apr;47(4):508-15
21691261
Blood. 2012 Feb 9;119(6):1590-8
22184406
Biol Blood Marrow Transplant. 2013 Oct;19(10):1465-73
23879970
Science. 2002 Mar 15;295(5562):2097-100
11896281
Br J Haematol. 1986 Jun;63(2):221-30
3521712
Blood. 2010 Jun 10;115(23):4934-43
20200356
Blood. 2011 Dec 15;118(25):6691-7
21940825
Blood. 1991 Oct 15;78(8):2120-30
1912589
Bone Marrow Transplant. 2004 Apr;33(7):729-34
14755315
Exp Hematol. 2006 Jan;34(1):66-71
16413392
J Immunol. 2005 Jan 15;174(2):752-7
15634895
Transplantation. 2008 Sep 15;86(5):686-96
18791450
Bone Marrow Transplant. 2016 May;51(5):687-91
26855158
Bone Marrow Transplant. 1987 Oct;2(3):279-85
3332176
Haematologica. 2006 Jul;91(7):935-40
16818281
J Exp Med. 1987 Apr 1;165(4):1212-7
3549961
Blood. 2006 Jan 1;107(1):167-75
16131564
Blood. 2011 Nov 24;118(22):5957-64
21967975
PLoS Med. 2008 Jan 29;5(1):e26
18232731
Bone Marrow Transplant. 2016 Feb;51(2):249-55
26437066
Exp Hematol. 2004 Dec;32(12):1163-72
15588941
Nature. 2006 Jun 29;441(7097):1075-9
16810242
Blood. 2013 May 2;121(18):3578-85
23487025
Blood. 2006 Feb 15;107(4):1724-30
16239425
Leukemia. 2007 Aug;21(8):1733-8
17541394
J Immunol. 1992 May 1;148(9):2953-60
1573278
Biol Blood Marrow Transplant. 2012 Sep;18(9):1446-54
22449610
Blood. 1989 Oct;74(5):1477-80
2790180
Blood. 2003 May 15;101(10):3991-9
12521999
Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10695-9
7524102
J Immunol. 1984 Aug;133(2):769-74
6203978
Blood. 2007 Feb 1;109(3):1307-15
17018854
Eur J Immunol. 2002 Mar;32(3):793-9
11870623
Blood. 1989 Nov 1;74(6):2227-36
2804361