Pillai A, Teo P, George T, Mukhopadhyay A, Dejbakhsh-Jones S, Strober S
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5166, USA.
Bone Marrow Transplant. 2007 Sep;40(5):487-97. doi: 10.1038/sj.bmt.1705759. Epub 2007 Jul 2.
The goal of the current study was to determine whether whole bone marrow cells or splenic CD8(+) T cells from C57BL/6 (H-2(b)) donor mice, which are tolerant to BALB/c (H-2(d)) alloantigens, are capable of mediating graft anti-tumor activity against a BALB/c B-cell lymphoma after injection into irradiated BALB/c hosts. The experimental results show that high doses of splenic CD8(+) T cells mixed with T cell-depleted bone marrow cells from C57BL/6 non-tolerant (normal) donors eliminate the BCL(1) B-cell lymphoma cells and induce lethal graft-versus-host disease (GVHD). CD8(+) T cells from tolerant donors simultaneously lose both their ability to induce GVHD and their anti-tumor activity. Whole bone marrow cell transplants from normal donors eliminated BCL(1) tumor cells without inducing GVHD, and bone marrow cells from tolerant donors failed to eliminate the tumor cells. The infused BCL(1) tumor cells expressed an immunogenic tumor-specific idiotype antigen disparate from host alloantigens, indicating that recognition of the tumor-specific antigen alone was insufficient to elicit graft anti-tumor activity from unimmunized allotolerant donor splenic CD8(+) T cells or whole bone marrow cells. We conclude that CD8(+) T cells from unimmunized normal donor mice require alloantigen recognition to mediate their anti-tumor activity following allogeneic BMT.
本研究的目的是确定来自对BALB/c(H-2(d))同种异体抗原耐受的C57BL/6(H-2(b))供体小鼠的全骨髓细胞或脾CD8(+) T细胞,在注入经照射的BALB/c宿主后,是否能够介导针对BALB/c B细胞淋巴瘤的移植物抗肿瘤活性。实验结果表明,高剂量的脾CD8(+) T细胞与来自C57BL/6非耐受(正常)供体的T细胞耗竭的骨髓细胞混合,可消除BCL(1) B细胞淋巴瘤细胞并诱发致死性移植物抗宿主病(GVHD)。来自耐受供体的CD8(+) T细胞同时失去了诱导GVHD的能力和抗肿瘤活性。来自正常供体的全骨髓细胞移植可消除BCL(1)肿瘤细胞而不诱发GVHD,而来自耐受供体的骨髓细胞则无法消除肿瘤细胞。注入的BCL(1)肿瘤细胞表达了一种与宿主同种异体抗原不同的免疫原性肿瘤特异性独特型抗原,这表明仅识别肿瘤特异性抗原不足以从未免疫的同种异体耐受供体脾CD8(+) T细胞或全骨髓细胞中引发移植物抗肿瘤活性。我们得出结论,来自未免疫正常供体小鼠的CD8(+) T细胞在异基因骨髓移植后需要识别同种异体抗原才能介导其抗肿瘤活性。