Hirano A, Luke P P, Specht S M, Fraser M O, Takayama T, Lu L, Hoffman R, Thomson A W, Jordan M L
Department of Urology, University of Pittsburgh Medical Center and Veterans Administration Medical Center, PA, USA.
Transpl Immunol. 2000 Nov;8(3):161-8. doi: 10.1016/s0966-3274(00)00022-8.
Immature dendritic cells (DCs) are deficient in surface co-stimulatory molecules and have been shown to exhibit a 'tolerogenic' potential. We investigated the allostimulatory activity of immature DCs in one-way mixed leukocyte reactions and their capacity to inhibit anti-donor cytolytic activity in the sponge matrix allograft model. Immature DCs (CD80 and CD86 deficient) were derived from bone marrow cells propagated in GM-CSF and TGF-beta1. Mature DCs (CD80+ and CD86+) were derived from bone marrow cells propagated in GM-CSF and IL-4. Either 2 x 10(6) DBA/2J (DBA, H-2d) immature DCs or 2 x 10(6) mature DCs were injected intravenously into C57BL/6J (B6, H-2b) mice 7 days prior to sponge matrix allograft implantation. On day 12, the sponge was harvested and the graft-infiltrating cells were tested in vitro for cytotoxic T lymphocyte (CTL) activity. Immature dendritic cell (DC) infused significantly and markedly inhibited intra-graft CTL activity compared to mature DCs and syngeneic bone marrow control cells. The administration of immature DCs directly into the sponge allograft failed to induce hyporeactivity. Thus, the only systemic infusion of immature donor DCs was able to recapitulate the donor-specific transfusion effect, and the capacity of donor bone marrow cells to induce donor-specific hyporeactivity in the sponge allograft model.
未成熟树突状细胞（DCs）表面共刺激分子缺乏，且已显示出具有“致耐受性”潜能。我们研究了未成熟DCs在单向混合淋巴细胞反应中的同种异体刺激活性，以及它们在海绵基质同种异体移植模型中抑制抗供体细胞溶解活性的能力。未成熟DCs（缺乏CD80和CD86）来源于在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和转化生长因子-β1（TGF-β1）中培养的骨髓细胞。成熟DCs（CD80+和CD86+）来源于在GM-CSF和白细胞介素-4（IL-4）中培养的骨髓细胞。在海绵基质同种异体移植植入前7天，将2×10⁶个DBA/2J（DBA，H-2d）未成熟DCs或2×10⁶个成熟DCs静脉注射到C57BL/6J（B6，H-2b）小鼠体内。在第12天，收获海绵，并在体外检测移植物浸润细胞的细胞毒性T淋巴细胞（CTL）活性。与成熟DCs和同基因骨髓对照细胞相比，注入未成熟树突状细胞（DC）显著且明显地抑制了移植物内的CTL活性。将未成熟DCs直接注入海绵同种异体移植中未能诱导低反应性。因此，仅全身输注未成熟供体DCs就能重现供体特异性输血效应，以及供体骨髓细胞在海绵同种异体移植模型中诱导供体特异性低反应性的能力。
