Amplification of Autoimmune Response through Induction of Dendiritic Cell Maturation in Inflamed Tissues

被引:59
作者
Melli, Kristin [1 ]
Friedman, Rachel S. [2 ]
Martin, Ashley E. [1 ]
Finger, Erik B. [1 ]
Miao, Gang [1 ]
Szot, Gregory L. [3 ]
Krummel, Matthew F. [2 ]
Tang, Qizhi [1 ]
机构
[1] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Univ Calif Diabet Ctr, Dept Med, San Francisco, CA 94143 USA
关键词
GREEN FLUORESCENT PROTEIN; NONOBESE DIABETIC MOUSE; DENDRITIC CELLS; T-CELLS; IN-VIVO; BETA-CELLS; NOD MICE; SELF-ANTIGENS; LYMPH-NODE; ISLETS;
D O I
10.4049/jimmunol.0803543
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing beta cells in the islets of Langerhans in type 1 diabetes. in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed beta cell-derived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40(high) intra-islet DCs up-regulated CCR7, and a small number of CD40(high) DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes. The Journal of Immunology, 2009, 182: 2590-2600.
引用
收藏
页码:2590 / 2600
页数:11
相关论文
共 45 条
[1]   Effect of pH on thermal- and chemical-induced denaturation of GFP [J].
Alkaabi, KM ;
Yafea, A ;
Ashraf, SS .
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 2005, 126 (02) :149-156
[2]   The NOD mouse: A model of immune dysregulation [J].
Anderson, MS ;
Bluestone, JA .
ANNUAL REVIEW OF IMMUNOLOGY, 2005, 23 :447-485
[3]   A noninvasive cell-based assay for monitoring proteolytic activity within a specific subcellular compartment [J].
Belkhiri, A ;
Lytvyn, V ;
Guilbault, C ;
Bourget, L ;
Massie, B ;
Nägler, DK ;
Ménard, R .
ANALYTICAL BIOCHEMISTRY, 2002, 306 (02) :237-246
[4]   Dendritic cells in islets of Langerhans constitutively present β cell-derived peptides bound to their class II MHC molecules [J].
Calderon, Boris ;
Suri, Anish ;
Miller, Mark J. ;
Unanue, Emil R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (16) :6121-6126
[5]   Studies in B7-deficient mice reveal a critical role for B7 costimulation in both induction and effector phases of experimental autoimmune encephalomyelitis [J].
Chang, TT ;
Jabs, C ;
Sobel, RA ;
Kuchroo, VK ;
Sharpe, AH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (05) :733-740
[6]   TOLERANCE INDUCTION TO CULTURED ISLET ALLOGRAFTS .1. CHARACTERIZATION OF THE TOLERANT STATE [J].
COULOMBE, M ;
GILL, RG .
TRANSPLANTATION, 1994, 57 (08) :1195-1200
[7]   Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney [J].
Dong, XY ;
Swaminathan, S ;
Bachman, LA ;
Croatt, AJ ;
Nath, KA ;
Griffin, MD .
KIDNEY INTERNATIONAL, 2005, 68 (03) :1096-1108
[8]   Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway [J].
Fife, Brian T. ;
Guleria, Indira ;
Bupp, Melanie Gubbels ;
Eagar, Todd N. ;
Tang, Qizhi ;
Bour-Jordan, Helene ;
Yagita, Hideo ;
Azuma, Miyuki ;
Sayegh, Mohamed H. ;
Bluestone, Jeffrey A. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (12) :2737-2747
[9]   TEMPORAL CHANGES IN PANCREATIC-ISLET COMPOSITION IN C57BL 6J-DB/DB (DIABETES) MICE [J].
GAPP, DA ;
LEITER, EH ;
COLEMAN, DL ;
SCHWIZER, RW .
DIABETOLOGIA, 1983, 25 (05) :439-443
[10]   Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development [J].
Gregori, S ;
Giarratana, N ;
Smiroldo, S ;
Adorini, L .
JOURNAL OF IMMUNOLOGY, 2003, 171 (08) :4040-4047