Cross-tolerance of recipient-derived transforming growth factor-beta dendritic cells.
Administration of donor-derived immature dendritic cells (DC) treated with transforming growth factor-beta (TGF-beta) to prevent allograft rejection is not applicable for clinical use. We therefore attempted to explore the use of recipient-derived DC pulsed with donor antigens via the indirect pathway (cross-priming). DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). TGF-beta (0.2 ng/mL) was added at the initiation of culture. The resultant TGF-beta DC were pulsed with B10 (H2(b)) splenocyte lysate. Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta. C3H DC pulsed with B10 antigens stimulated a proliferative response in C3H T cells which was inhibited when DC were treated with TGF-beta, and the cytotoxic T-lymphocyte (CTL) activity was also inhibited. This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production. A single injection of TGF-beta DC prolonged allograft survival (median survival time [MST] 18 days vs 10 days in no-DC treatment control; P < .05). These data indicated that an approach utilizing recipient DC as a "vaccine" strategy is possible.
Tiao
M-M
MM
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Lu
L
L
Huang
L-T
LT
Liang
C-D
CD
Chen
C-L
CL
Tao
R
R
Fung
J J
JJ
Qian
S
S
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology* / Q000637:transplantation*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis*; D023001:Transplantation Tolerance
D015703:Antigens, CD; D016212:Transforming Growth Factor beta