Neural progenitor cells lack immunogenicity and resist destruction as allografts

被引:127
作者
Hori, J
Ng, TF
Shatos, M
Klassen, H
Streilein, JW
Young, MJ
机构
[1] Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA
[2] Nippon Med Coll, Dept Ophthalmol, Tokyo, Japan
[3] Childrens Hosp Orange Cty, Stem Cell Res, Orange, CA 92668 USA
关键词
stem cells; transplantation; MHC; tolerance; suppression; anergy; neural;
D O I
10.1634/stemcells.21-4-405
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Multipotent, self-renewing stem and progenitor cells isolated from the mammalian central nervous system (CNS) have been shown to survive as allografts following transplantation to sites throughout the neuraxis. However, studies of this type shed little light upon the immunologic properties of the cells themselves, primarily because little is learned about the intrinsic immunogenic properties of a cell when it is grafted into an immune-privileged site. We have therefore investigated the immunogenic and antigenic properties of CNS progenitor cells by grafting them into a conventional (i.e., non-immune-privileged) site, namely, beneath the kidney capsule. Our results indicate that allogeneic CNS progenitor cells survive at least 4 weeks in a conventional site, during which time they neither sensitize their hosts nor express detectable levels of major histocompatibility complex (MHC) class I or II. These in vivo data are in accord with flow cytometric results showing that CNS progenitor cells do not express MHC class I or class II, either at baseline or upon differentiation in 10% serum. Exposure to interferon gamma, however, reversibly upregulates expression of these key transplantation antigens. Together, these results reveal CNS progenitor cells to possess inherent immune privilege. Since CNS progenitor cell allografts were rejected beneath the kidney capsule following specific sensitization of the host, CNS progenitor cells were able to display alloantigens, albeit not in an immunogenic form.
引用
收藏
页码:405 / 416
页数:12
相关论文
共 32 条
[1]   A ROLE FOR CD95 LIGAND IN PREVENTING GRAFT-REJECTION [J].
BELLGRAU, D ;
GOLD, D ;
SELAWRY, H ;
MOORE, J ;
FRANZUSOFF, A ;
DUKE, RC .
NATURE, 1995, 377 (6550) :630-632
[2]   Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo [J].
Bjornson, CRR ;
Rietze, RL ;
Reynolds, BA ;
Magli, MC ;
Vescovi, AL .
SCIENCE, 1999, 283 (5401) :534-537
[3]   Generalized potential of adult neural stem cells [J].
Clarke, DL ;
Johansson, CB ;
Wilbertz, J ;
Veress, B ;
Nilsson, E ;
Karlström, H ;
Lendahl, U ;
Frisén, J .
SCIENCE, 2000, 288 (5471) :1660-1663
[4]  
Dong YS, 1999, J IMMUNOL, V162, P4731
[5]   EXPRESSION OF CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS ON REACTIVE ASTROCYTES AND ENDOTHELIAL-CELLS WITHIN THE GLIOSIS SURROUNDING METASTASES AND ABSCESSES [J].
FRANK, E ;
PULVER, M ;
DETRIBOLET, N .
JOURNAL OF NEUROIMMUNOLOGY, 1986, 12 (01) :29-36
[6]   Transplantation of embryonic dopamine neurons for severe Parkinson's disease. [J].
Freed, CR ;
Greene, PE ;
Breeze, RE ;
Tsai, WY ;
DuMouchel, W ;
Kao, R ;
Dillon, S ;
Winfield, H ;
Culver, S ;
Trojanowski, JQ ;
Eidelberg, D ;
Fahn, S .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (10) :710-719
[7]   ISOLATION, CHARACTERIZATION, AND USE OF STEM-CELLS FROM THE CNS [J].
GAGE, FH ;
RAY, J ;
FISHER, LJ .
ANNUAL REVIEW OF NEUROSCIENCE, 1995, 18 :159-192
[8]   IMMUNOHISTOCHEMICAL STUDIES OF ADULT HUMAN GLIAL-CELLS [J].
GRENIER, Y ;
RUIJS, TCG ;
ROBITAILLE, Y ;
OLIVIER, A ;
ANTEL, JP .
JOURNAL OF NEUROIMMUNOLOGY, 1989, 21 (2-3) :103-115
[9]   Sequential bilateral transplantation in Parkinson's disease -: Effects of the second graft [J].
Hagell, P ;
Schrag, A ;
Piccini, P ;
Jahanshahi, M ;
Brown, R ;
Rehncrona, S ;
Widner, H ;
Brundin, P ;
Rothwell, JC ;
Odin, P ;
Wenning, GK ;
Morrish, P ;
Gustavii, B ;
Björklund, A ;
Brooks, DJ ;
Marsden, CD ;
Quinn, NP ;
Lindvall, O .
BRAIN, 1999, 122 :1121-1132
[10]   Astrocytic factors down-regulate the expression of major histocompatibility complex-class-II and intercellular adhesion molecule-1 on human monocytes [J].
Hailer, NP ;
Glomsda, B ;
Blaheta, RA .
NEUROSCIENCE LETTERS, 2001, 298 (01) :33-36