Rejection and regulation: a tight balance

被引:13
作者
Ashoor, Isa F.
Najafian, Nader
机构
[1] Childrens Hosp, Div Nephrol, Brigham & Womens Hosp, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
关键词
allograft rejection; allograft tolerance; regulatory cells; transplantation; TOLEROGENIC DENDRITIC CELLS; ACUTE CELLULAR REJECTION; T-CELL; B-CELLS; TH17; CELLS; COSTIMULATORY PATHWAYS; TRANSPLANT TOLERANCE; EMERGING ROLE; SURVIVAL; INDUCTION;
D O I
10.1097/MOT.0b013e32834ef52a
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Purpose of review Achieving allograft tolerance is the holy grail of transplantation. However, tolerance and rejection are two extreme ends of a scale that can be tipped in either direction. We review the novel effector and regulatory mechanisms involved and factors that tip the balance in favor of rejection or regulation. Recent findings It is increasingly recognized that established T-cell phenotypes could change their commitments. New data point to the plasticity of Th17 cells in vivo with a reciprocal balance of Th17 cells and regulatory T cells (Tregs) driven by the local cytokine environment. Treg-cell profiles have been linked to acute and chronic allograft outcomes, and emerging data also indicate a novel role of a regulatory B-cell population. Current research efforts are looking into factors that tip the balance toward allograft tolerance by targeting cytokines, novel costimulatory pathways such as T-cell immunoglobulin mucin molecules, and components of innate immunity, particularly dendritic cells. Summary The balance of effector and regulatory mechanisms contributing to allograft outcome is very complex. It is likely that targeting multiple pathways will be required to achieve tolerance. Further studies are warranted to define this balance and identify optimal combination of therapeutic interventions.
引用
收藏
页码:1 / 7
页数:7
相关论文
共 66 条
[1]   Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells [J].
Anderson, Ana C. ;
Anderson, David E. ;
Bregoli, Lisa ;
Hastings, William D. ;
Kassam, Nasim ;
Lei, Charles ;
Chandwaskar, Rucha ;
Karman, Jozsef ;
Su, Ee W. ;
Hirashima, Mitsuomi ;
Bruce, Jeffrey N. ;
Kane, Lawrence P. ;
Kuchroo, Vijay K. ;
Hafler, David A. .
SCIENCE, 2007, 318 (5853) :1141-1143
[2]   Is monitoring of FOXP3 Treg cells in renal transplants during acute cellular rejection episodes useful? [J].
Batsford, S. ;
Dickenmann, M. ;
Duermueller, U. ;
Hopfer, H. ;
Gudat, F. ;
Mihatsch, M. .
CLINICAL NEPHROLOGY, 2011, 75 (02) :101-106
[3]   Costimulatory blockade with mTor inhibition abrogates effector T-cell responses allowing regulatory T-cell survival in renal transplantation [J].
Bestard, Oriol ;
Cassis, Linda ;
Cruzado, Josep M. ;
Torras, Joan ;
Franquesa, Marcella ;
Gil-Vernet, Salvador ;
Lucia, Marc ;
Grinyo, Josep M. .
TRANSPLANT INTERNATIONAL, 2011, 24 (05) :451-460
[4]   Decreased Percentage of CD4+ FoxP3+ Cells in Bronchoalveolar Lavage From Lung Transplant Recipients Correlates With Development of Bronchiolitis Obliterans Syndrome [J].
Bhorade, Sangeeta M. ;
Chen, Hong ;
Molinero, Luciana ;
Liao, Chuanhong ;
Garrity, Edward R. ;
Vigneswaran, Wickii T. ;
Shilling, Rebecca ;
Sperling, Anne ;
Chong, Anita ;
Alegre, Maria-Luisa .
TRANSPLANTATION, 2010, 90 (05) :540-546
[5]   ACTIVELY ACQUIRED TOLERANCE OF FOREIGN CELLS [J].
BILLINGHAM, RE ;
BRENT, L ;
MEDAWAR, PB .
NATURE, 1953, 172 (4379) :603-606
[6]  
Boenisch O, 2011, AM J TRANSPLANT, V11, P28
[7]   Negative T-cell costimulatory pathways: their role in regulating alloimmune responses [J].
Boenisch, Olaf ;
Sayegh, Mohamed H. ;
Najafian, Nader .
CURRENT OPINION IN ORGAN TRANSPLANTATION, 2008, 13 (04) :373-378
[8]   TIM-3: A Novel Regulatory Molecule of Alloimmune Activation [J].
Boenisch, Olaf ;
D'Addio, Francesca ;
Watanabe, Toshihiko ;
Elyaman, Wassim ;
Magee, Ciara N. ;
Yeung, Melissa Y. ;
Padera, Robert F. ;
Rodig, Scott J. ;
Murayama, Takaya ;
Tanaka, Katsunori ;
Yuan, Xueli ;
Ueno, Takuya ;
Jurisch, Anke ;
Mfarrej, Bechara ;
Akiba, Hisaya ;
Yagita, Hideo ;
Najafian, Nader .
JOURNAL OF IMMUNOLOGY, 2010, 185 (10) :5806-5819
[9]   Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA) [J].
Burmester, Gerd R. ;
Feist, E. ;
Kellner, H. ;
Braun, J. ;
Iking-Konert, C. ;
Rubbert-Roth, A. .
ANNALS OF THE RHEUMATIC DISEASES, 2011, 70 (05) :755-759
[10]   Mice Lacking Endogenous IL-10-Producing Regulatory B Cells Develop Exacerbated Disease and Present with an Increased Frequency of Th1/Th17 but a Decrease in Regulatory T Cells [J].
Carter, Natalie A. ;
Vasconcellos, Rita ;
Rosser, Elizabeth C. ;
Tulone, Calogero ;
Munoz-Suano, Alba ;
Kamanaka, Masahito ;
Ehrenstein, Michael R. ;
Flavell, Richard A. ;
Mauri, Claudia .
JOURNAL OF IMMUNOLOGY, 2011, 186 (10) :5569-5579