Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD154 monoclonal antibody

被引:39
作者
Gordon, EJ
Markees, TG
Phillips, NE
Noelle, RJ
Shultz, LD
Mordes, JP
Rossini, AA
Greiner, DL
机构
[1] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA
[2] Dartmouth Med Sch, Dept Microbiol, Lebanon, NH USA
[3] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
D O I
10.2337/diabetes.47.8.1199
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and a brief course of anti-CD154 (anti-CD40 ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive for similar to 50 days without further intervention. We now report adaptation of this protocol to the transplantation of islet and skin xenografts. We observed prolonged survival of rat islet xenografts in mice treated with donor-specific spleen cell transfusion and anti-CD154 monoclonal antibody (mAb). Challenge islet xenografts placed on these animals indicated that graft acceptance was species-specific but not strain specific. Spleen cells from recipients bearing intact grafts led to rejection of rat islet xenografts in scid mice, suggesting that graft acceptance was not due to complete clonal deletion of xenoreactive cells. We also observed prolonged survival of rat skin xenografts in mice treated with donor-specific transfusion and antiCD154 mAb. Prolonged survival of skin xenografts was also species specific. We conclude that treatment with appropriately timed donor-specific transfusion and anti-CD154 mAb induces durable survival of both islet and skin xenografts in mice. Because this procedure is targeted directly at CD154, a co-activation molecule expressed predominantly by activated CD4(+) T-cells, the results suggest that CD4(+) cells have a major role in the cellular immune response to xenografts.
引用
收藏
页码:1199 / 1206
页数:8
相关论文
共 40 条
[21]   XENOTRANSPLANTATION [J].
LU, CY ;
KHAIRELDIN, TA ;
DAWIDSON, IA ;
BUTLER, TM ;
BRASKY, KM ;
VAZQUEZ, MA ;
SICHER, SC .
FASEB JOURNAL, 1994, 8 (14) :1122-1130
[22]  
MANDEL TE, 1992, TRANSPLANT P, V24, P216
[23]  
Markees TG, 1996, TRANSPLANT P, V28, P814
[24]   Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4+ T cells, interferon-γ, and CTLA4 [J].
Markees, TG ;
Phillips, NE ;
Gordon, EJ ;
Noelle, RJ ;
Shultz, LD ;
Mordes, JP ;
Greiner, DL ;
Rossini, AA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2446-2455
[25]   Prolonged survival of mouse skin allografts in recipients treated with donor splenocytes and antibody to CD40 ligand [J].
Markees, TG ;
Phillips, NE ;
Noelle, RJ ;
Shultz, LD ;
Mordes, JP ;
Greiner, DL ;
Rossini, AA .
TRANSPLANTATION, 1997, 64 (02) :329-335
[26]  
MATTHEWS DE, 1988, USING UNDERSTANDING, P79
[27]  
MAYO GL, 1994, TRANSPLANTATION, V58, P107
[28]  
MORRIS CF, 1995, J IMMUNOL, V154, P2470
[29]   A 39-KDA PROTEIN ON ACTIVATED HELPER T-CELLS BINDS CD40 AND TRANSDUCES THE SIGNAL FOR COGNATE ACTIVATION OF B-CELLS [J].
NOELLE, RJ ;
ROY, M ;
SHEPHERD, DM ;
STAMENKOVIC, I ;
LEDBETTER, JA ;
ARUFFO, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (14) :6550-6554
[30]   SURVIVAL OF MOUSE PANCREATIC-ISLET ALLOGRAFTS IN RECIPIENTS TREATED WITH ALLOGENEIC SMALL LYMPHOCYTES AND ANTIBODY TO CD40 LIGAND [J].
PARKER, DC ;
GREINER, DL ;
PHILLIPS, NE ;
APPEL, MC ;
STEELE, AW ;
DURIE, FH ;
NOELLE, RJ ;
MORDES, JP ;
ROSSINI, AA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (21) :9560-9564