Protective immunity induced by B7/CD28-costimulated gamma delta T cells to the EL-4 lymphoma in allogenic athymic mice.
Protective immunity induced by B7/CD28-costimulated gamma delta T cells to the EL-4 lymphoma in allogenic athymic mice.
复制标题
B7/CD28 共刺激的 γ δ T 细胞在同种异体无胸腺小鼠中诱导对 EL-4 淋巴瘤的保护性免疫。
作者：
Y. Li;S. A. Newby;J. Johnston;K. Hellström;L. Chen
我们以前报道过用含有鼠B7-1基因的逆转录病毒（B7+ EL-4）转导的鼠EL-4淋巴瘤（H-2b）在同种异体BALB/c（nu/nu）无胸腺小鼠（H-2d）中短暂生长数周，随后消退。相比之下，我们现在表明，B7+ EL-4细胞在几种联合免疫缺陷小鼠（包括SCID和NIH III小鼠）中进行性生长，这些小鼠缺乏表达TCR-α β或-γ δ的T细胞。此外，用特异性mAb耗尽γ δ T细胞使得B7+ EL-4细胞在90%的无胸腺小鼠中的进行性生长成为可能，而耗尽α β T细胞使得这些小鼠中的50%的肿瘤生长成为可能。用B7+ EL-4细胞免疫无胸腺小鼠可以防止野生型B7- EL-4细胞的生长。这种保护性免疫通过用抗TCR-γ δ mAb的体内治疗而被消除，进一步表明γ δ T细胞在无胸腺小鼠的肿瘤排斥中起重要作用。用经辐照的B7 + EL-4细胞在体外反复再刺激B7 + EL-4免疫的无胸腺小鼠，建立γ δ T细胞系Tc 1。当针对广谱靶细胞进行测试时，Tc 1裂解几种小鼠淋巴瘤细胞系，但不裂解其他肿瘤细胞系，这表明Tc 1识别的Ag具有有限的分布。我们的数据表明，γ δ T细胞，并在较小程度上，胸腺外α β T细胞，介导对B7+ EL-4细胞在同种异体无胸腺小鼠的免疫应答。
We previously reported that the murine EL-4 lymphoma (H-2b) transduced with a retrovirus containing the murine B7-1 gene (B7+ EL-4) grew transiently for several weeks and subsequently regressed in allogenic BALB/c (nu/nu) athymic mice (H-2d). We now show that, in contrast, B7+ EL-4 cells grow progressively in several combined immunodeficiency mice, including SCID and NIH III mice, which lack T cells expressing either TCR-alpha beta or -gamma delta. Furthermore, depletion of gamma delta T cells with a specific mAb made possible the progressive growth of B7+ EL-4 cells in 90% of athymic mice while depletion of alpha beta T cells allowed tumor growth in 50% of these mice. Immunization of athymic mice with B7+ EL-4 cells prevented the outgrowth of wild-type B7- EL-4 cells. This protective immunity was abrogated by in vivo treatment with an anti-TCR-gamma delta mAb, further indicating that gamma delta T cells play an important role in tumor rejection by athymic mice. A gamma delta T cell line, Tc1, was established from B7+ EL-4-immunized athymic mice by repeated restimulation in vitro with irradiated B7+ EL-4 cells. When tested against a broad spectrum of target cells, Tc1 lysed several murine lymphoma lines, but did not lyse other tumor lines, suggesting that the Ag recognized by Tc1 has a limited distribution. Our data demonstrate that gamma delta T cells, and, to a less extent, extrathymic alpha beta T cells, mediate an immune response against B7+ EL-4 cells in allogeneic athymic mice.