Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches

被引:22
作者
Chidgey, Ann P. [1 ]
Seach, Natalie [1 ]
Dudakov, Jarrod [1 ]
Hammett, Maree V. [1 ]
Boyd, Richard L. [1 ]
机构
[1] Monash Univ, STRIP, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia
基金
英国医学研究理事会;
关键词
Thymus; Ageing; Regeneration; Stem cells; Immune reconstitution;
D O I
10.1007/s00281-008-0140-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Poor immune recovery is characteristic of bone marrow transplantation and leads to high levels of morbidity and mortality. The primary underlying cause is a compromised thymic function, resulting from age-induced atrophy and further compounded by the damaging effects of cytoablative conditioning regimes on thymic epithelial cells (TEC). Several strategies have been proposed to enhance T cell reconstitution. Some, such as the use of single biological agents, are currently being tested in clinical trials. However, a more rational approach to immune restoration will be to leverage the evolving repertoire of new technologies. Specifically, the combined targeting of TEC, thymocytes and peripheral T cells, together with the bone marrow niches, promises a more strategic clinical therapeutic platform.
引用
收藏
页码:457 / 477
页数:21
相关论文
共 228 条
[1]   Interleukin 2 regulation following semi-allogeneic bone marrow transplantation in mice [J].
Abdul-Hai, Ali ;
Ben-Yehuda, Arie ;
Galsky, Haya ;
Slavin, Shimon ;
Or, Reuven .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2006, 55 (11) :1330-1336
[2]   Presence of nerve growth factor in the thymus of prenatal, postnatal and pregnant rats [J].
Aloe, L ;
Micera, A ;
Bracci-Laudiero, L ;
Vigneti, E ;
Turrini, P .
THYMUS, 1997, 24 (04) :221-231
[3]   Keratinocyte growth factor (KGF) is required for postnatal thymic regeneration [J].
Alpdogan, Ö ;
Hubbard, VM ;
Smith, OM ;
Patel, N ;
Lu, S ;
Goldberg, GL ;
Gray, DH ;
Feinman, J ;
Kochman, AA ;
Eng, JM ;
Suh, D ;
Muriglan, SJ ;
Boyd, RL ;
van den Brink, MRM .
BLOOD, 2006, 107 (06) :2453-2460
[4]   Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease [J].
Alpdogan, O ;
Schmaltz, C ;
Muriglan, SJ ;
Kappel, BJ ;
Perales, MA ;
Rotolo, JA ;
Halm, JA ;
Rich, BE ;
van den Brink, MRM .
BLOOD, 2001, 98 (07) :2256-2265
[5]   IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation [J].
Alpdogan, Ö ;
Muriglan, SJ ;
Eng, JM ;
Willis, LM ;
Greenberg, AS ;
Kappel, B ;
van den Brink, MRM .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (07) :1095-1107
[6]   Projection of an immunological self shadow within the thymus by the aire protein [J].
Anderson, MS ;
Venanzi, ES ;
Klein, L ;
Chen, ZB ;
Berzins, SP ;
Turley, SJ ;
von Boehmer, H ;
Bronson, R ;
Dierich, A ;
Benoist, C ;
Mathis, D .
SCIENCE, 2002, 298 (5597) :1395-1401
[7]   Age-associated thymic atrophy is linked to a decline in IL-7 production [J].
Andrew, D ;
Aspinall, R .
EXPERIMENTAL GERONTOLOGY, 2002, 37 (2-3) :455-463
[8]   Thymic atrophy in the mouse is a soluble problem of the thymic environment [J].
Aspinall, R ;
Andrew, D .
VACCINE, 2000, 18 (16) :1629-1637
[9]   Thymic involution in aging [J].
Aspinall, R ;
Andrew, D .
JOURNAL OF CLINICAL IMMUNOLOGY, 2000, 20 (04) :250-256
[10]   Old rhesus macaques treated with interleukin-7 show increased TREC levels and respond well to influenza vaccination [J].
Aspinall, Richard ;
Pido-Lopez, Jeffrey ;
Imami, Nesrina ;
Henson, Sian M. ;
Ngom, Pa Tamba ;
Morre, Michel ;
NiphuiS, Henk ;
Remarque, Ed ;
Rosenwirth, Brigitte ;
Heeney, Jonathan L. .
REJUVENATION RESEARCH, 2007, 10 (01) :5-17