IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants

被引:326
作者
Burlingham, William J.
Love, Robert B.
Jankowska-Gan, Ewa
Haynes, Lynn D.
Xu, Qingyong
Bobadilla, Joseph L.
Meyer, Keith C.
Hayney, Mary S.
Braun, Ruedi K.
Greenspan, Daniel S.
Gopalakrishnan, Bagavathi
Cai, Junchao
Brand, David D.
Yoshida, Shigetoshi
Cummings, Oscar W.
Willkes, David S.
机构
[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Transplant Div, Madison, WI 53792 USA
[2] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA
[3] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA
[4] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA
[5] Terasaki Fdn Lab, Los Angeles, CA USA
[6] Vet Affairs Med Ctr, Dept Med, Memphis, TN USA
[7] Univ Tennessee, Memphis, TN USA
[8] Indiana Univ Sch Med, Ctr Immunobiol, Dept Med, Indianapolis, IN USA
[9] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA
关键词
D O I
10.1172/JCI28031
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 [基础医学];
摘要
Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(V)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4(+) T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1 beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloinimunity initiates lung transplant rejection, de novo autoinummity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration.
引用
收藏
页码:3498 / 3506
页数:9
相关论文
共 44 条
[1]
Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells [J].
Acosta-Rodriguez, Eva V. ;
Rivino, Laura ;
Geginat, Jens ;
Jarrossay, David ;
Gattorno, Marco ;
Lanzavecchia, Antonio ;
Sallusto, Federica ;
Napolitani, Giorgio .
NATURE IMMUNOLOGY, 2007, 8 (06) :639-646
[2]
ACOSTARODRIGUEZ EV, 2007, IN PRESS NAT IMMUNOL
[3]
The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease [J].
Afzali, B. ;
Lombardi, G. ;
Lechler, R. I. ;
Lord, G. M. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2007, 148 (01) :32-46
[4]
Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates [J].
Azimzadeh, AM ;
Pfeiffer, S ;
Wu, GS ;
Schröder, C ;
Zhou, H ;
Zorn, GL ;
Kehry, M ;
Miller, GG ;
Rose, ML ;
Pierson, RN .
AMERICAN JOURNAL OF TRANSPLANTATION, 2005, 5 (10) :2349-2359
[5]
CD4+25+ regulatory T cells limit Th1-autoimmunity by inducing IL-10 producing T cells following human lung transplantation [J].
Bharat, A. ;
Fields, R. C. ;
Steward, N. ;
Trulock, E. P. ;
Patterson, G. A. ;
Mohanakumar, T. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (08) :1799-1808
[6]
COLLAGEN TYPE-I AND TYPE-V ARE PRESENT IN THE SAME FIBRIL IN THE AVIAN CORNEAL STROMA [J].
BIRK, DE ;
FITCH, JM ;
BABIARZ, JP ;
LINSENMAYER, TF .
JOURNAL OF CELL BIOLOGY, 1988, 106 (03) :999-1008
[7]
Cytokine regulation in RA synovial tissue: role of T cell/macrophage contact-dependent interactions [J].
Brennan, Fionula Mary ;
Foey, Andrew David .
ARTHRITIS RESEARCH & THERAPY, 2002, 4 (Suppl 3) :S177-S182
[8]
POST-TRANSPLANT OBLITERATIVE BRONCHIOLITIS AND OTHER LATE LUNG SEQUELAE IN HUMAN HEART-LUNG TRANSPLANTATION [J].
BURKE, CM ;
THEODORE, J ;
DAWKINS, KD ;
YOUSEM, SA ;
BLANK, N ;
BILLINGHAM, ME ;
VANKESSEL, A ;
JAMIESON, SW ;
OYER, PE ;
BALDWIN, JC ;
STINSON, EB ;
SHUMWAY, NE ;
ROBIN, ED .
CHEST, 1984, 86 (06) :824-829
[9]
Burlingham WJ, 2005, MEASURING IMMUNITY: BASIC BIOLOGY AND CLINICAL ASSESSMENT, P407, DOI 10.1016/B978-012455900-4/50297-X
[10]
Trans vivo analysis of human delayed-type hypersensitivity reactivity [J].
Carrodeguas, L ;
Orosz, CG ;
Waldman, WJ ;
Sedmak, DD ;
Adams, PW ;
VanBuskirk, AM .
HUMAN IMMUNOLOGY, 1999, 60 (08) :640-651