Indirect recognition of porcine swine leukocyte Ag class I molecules expressed on islets by human CD4+ T lymphocytes

被引:25
作者
Olack, B
Manna, P
Jaramillo, A
Steward, N
Swanson, C
Kaesberg, D
Poindexter, N
Howard, T
Mohanakumar, T
机构
[1] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
关键词
D O I
10.4049/jimmunol.165.3.1294
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Xenotransplantation of porcine islets is considered a viable alternative treatment for type 1 diabetes mellitus, Therefore, we characterized human PBL responding to porcine islets both in vitro by coculture and in vivo using SCID mice reconstituted with human PBLs (HuPBL-SCID) and transplanted with porcine islets. T cell lines generated in vitro and graft-infiltrating T cells obtained from HuPBL-SCID mice were CD4(+)-proliferated specifically to porcine islets cultured with autologous APC. This proliferation was abrogated by an anti-human class II Ab, These T cell lines also proliferated to purified swine leukocyte Ag (SLA) class I molecules in the presence of self-APC, indicating that the primary xenoantigens recognized are peptides derived from SLA, This CD4(+) T cell line lysed porcine islets but not splenocytes. CD4(+) T cell clones with Th0, Th1, and Th2 cytokine profiles were isolated. The Th0 and Th1 clones lysed porcine islets, whereas the Th2 clone that secreted a large amount of IL-4 was not lytic, These results demonstrate that human T cells responding to porcine islets are primarily CD4(+) and recognize porcine xenoantigens by the indirect Ag pathway presentation. These activated T cells produce cytokines that lyse islets, Furthermore, we demonstrate that the major porcine xenoantigens recognized are SLA class I molecules.
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页码:1294 / 1299
页数:6
相关论文
共 30 条
[1]   ANTI-CD4 MEDIATES CLONAL ANERGY DURING TRANSPLANTATION TOLERANCE INDUCTION [J].
ALTERS, SE ;
SHIZURU, JA ;
ACKERMAN, J ;
GROSSMAN, D ;
SEYDEL, KB ;
FATHMAN, CG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (02) :491-494
[2]   Xenogeneic transplantation [J].
Auchincloss, H ;
Sachs, DH .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :433-470
[3]   Delayed xenograft rejection [J].
Bach, FH ;
Winkler, H ;
Ferran, C ;
Hancock, WW ;
Robson, SC .
IMMUNOLOGY TODAY, 1996, 17 (08) :379-384
[4]  
BRETZEL RG, 1990, HORM METAB RES, V25, P128
[5]   T cell independence of macrophage and natural killer cell infiltration, cytokine production, and endothelial activation during delayed xenograft rejection [J].
Candinas, D ;
Belliveau, S ;
Koyamada, N ;
Miyatake, T ;
Hechenleitner, P ;
Mark, W ;
Bach, FH ;
Hancock, WW .
TRANSPLANTATION, 1996, 62 (12) :1920-1927
[6]   Prevention of the responses is critical for tolerance [J].
Chen, NX ;
Gao, QL ;
Field, EH .
TRANSPLANTATION, 1996, 61 (07) :1076-1083
[7]   Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells [J].
Delaney, CA ;
Pavlovic, D ;
Hoorens, A ;
Pipeleers, DG ;
Eizirik, DL .
ENDOCRINOLOGY, 1997, 138 (06) :2610-2614
[8]  
FALQUI L, 1991, TRANSPLANTATION, V51, P1322
[9]  
GILL RG, 1992, TRANSPLANT P, V24, P642
[10]   Resistance of established porcine islet xenografts to humoral rejection by hyperimmune sera [J].
Gourlay, WA ;
O'Neil, JJ ;
Hancock, WW ;
Monaco, AP ;
Maki, T .
TRANSPLANTATION, 1999, 68 (06) :888-893