Keratinocyte Growth Factor Improves Allogeneic Bone Marrow Engraftment through a CD4+Foxp3+ Regulatory T Cell-Dependent Mechanism

被引:7
作者
Bruinsma, Marieke [1 ]
van Soest, Peter L. [1 ]
Leenen, Pieter J. M. [2 ]
Lowenberg, Bob [1 ]
Cornelissen, Jan J. [1 ]
Braakman, Eric [1 ]
机构
[1] Erasmus Univ, Med Ctr, Dept Hematol, NL-3000 CA Rotterdam, Netherlands
[2] Erasmus Univ, Med Ctr, Dept Immunol, NL-3000 CA Rotterdam, Netherlands
关键词
VERSUS-HOST-DISEASE; DEFICIENT MICE; TRANSPLANTATION; REPAIR; PALIFERMIN; PROTECTION; EXPANSION; INJURY; MOUSE;
D O I
10.4049/jimmunol.0803253
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Keratinocyte growth factor (KGF) protects mice from acute graft-vs-host disease and graft rejection by cytoprotective and yet incompletely understood immunological mechanisms. Recently, we showed that administration of KGF induces selective peripheral expansion of CD4(+)Foxp3(+) regulatory T cells (Treg). In this study, we set out to assess whether the peripheral expansion of Treg accounts for the immunomodulatory effects of KGF after bone marrow (BM) transplantation. To exclude potentially confounding cytoprotective and thymopoietic effects of KGF, we applied KGF to congenic wild-type mice that served as T cell provider mice for T and B cell-deficient RAG-1(-/-) mice that were subsequently transplanted with allogeneic BM. Treatment of congenic T cell provider mice with KGF significantly improved engraftment and reduced graft rejection in BMT recipients. CD4(+)Foxp3(+) Treg remained increased for 4 wk, while expansion of congenic CD3(+) T cells was inhibited. To assess a causal relationship between expansion of Treg and improved BM engraftment, congenic Scurfy mice, which lack Foxp3(+) Treg, served as T cell provider mice and were treated with KGF. KGF-treatment of Scurfy mice did not affect engraftment nor did it inhibit the expansion of congenic T cells. These data demonstrate that administration of KGF to the T cell provider mice improves engraftment of allogeneic BM through a CD4(+)Foxp3(+) Treg-dependent mechanism. The Journal of Immunology, 2009, 182: 7364-7369.
引用
收藏
页码:7364 / 7369
页数:6
相关论文
共 26 条
[11]  
GODFREY VL, 1991, AM J PATHOL, V138, P1379
[12]   Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation [J].
Hoffmann, P ;
Ermann, J ;
Edinger, M ;
Fathman, CG ;
Strober, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) :389-399
[13]   Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes [J].
Joffre, O ;
Gorsse, N ;
Romagnoli, P ;
Hudrisier, D ;
van Meerwijk, JPM .
BLOOD, 2004, 103 (11) :4216-4221
[14]   Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation [J].
Min, DL ;
Taylor, PA ;
Panoskaltsis-Mortari, A ;
Chung, B ;
Danilenko, DM ;
Farrell, C ;
Lacey, DL ;
Blazar, BR ;
Weinberg, KI .
BLOOD, 2002, 99 (12) :4592-4600
[15]   Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging [J].
Min, Dullei ;
Panoskaltsis-Mortari, Angela ;
Kuro-o, Makoto ;
Hollaender, Georg A. ;
Blazar, Bruce R. ;
Weinberg, Kenneth I. .
BLOOD, 2007, 109 (06) :2529-2537
[16]   Role of naturally arising regulatory T cells in hematopoietic cell transplantation [J].
Nguyen, Vu H. ;
Zeiser, Robert ;
Negrin, Robert S. .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2006, 12 (10) :995-1009
[17]   Keratinocyte growth factor administered before conditioning ameliorates graft-versus-host disease after allogeneic bone marrow transplantation in mice [J].
Panoskaltsis-Mortari, A ;
Lacey, DL ;
Vallera, DA ;
Blazar, BR .
BLOOD, 1998, 92 (10) :3960-3967
[18]  
Panoskaltsis-Mortari A, 2000, BLOOD, V96, P4350
[19]   Clinical use of umbilical cord blood hematopoietic stem cells [J].
Rocha, V ;
Gluckman, E .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2006, 12 (01) :34-41
[20]   Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells [J].
Rossi, Simona W. ;
Jeker, Lukas T. ;
Ueno, Tomoo ;
Kuse, Sachiyo ;
Keller, Marcel P. ;
Zuklys, Saulius ;
Gudkov, Andrei V. ;
Takahama, Yousuke ;
Krenger, Werner ;
Blazar, Bruce R. ;
Hollaender, Georg A. .
BLOOD, 2007, 109 (09) :3803-3811