Choi Bo-Hwa, Kang Hyun-Kyu, Park Jung-Sun, Kim Sang-Ki, Pham Than-Nhan Nguyen, Zhu Xiao-Wei, Cho Duck, Nam Jong-Hee, Chung Ik-Joo, Kim Young-Jin, Rhee Joon-Haeng, Kim Hyeoung-Joon, Lee Je-Jung
Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
J Clin Apher. 2006 Dec;21(4):233-40. doi: 10.1002/jca.20105.
Clinical application of immunotherapy for acute myeloid leukemia (AML) requires the efficient induction of dendritic cells (DCs) from AML blast cells using in vitro culture. We examined the effect of autologous serum on the properties of leukemic DCs derived from leukemic cells of AML patients by culture in AIM-V medium with GM-CSF, IL-4, TNF-alpha, and 0, 2, 5, or 10% human autologous serum. The expressions of CD80, CD83, CD86, and HLA-DR were upregulated under all culture conditions; however, 10% autologous serum induced the highest expression levels of several molecules. The capacity of leukemic DCs to stimulate allogeneic T cells increased with increasing serum concentration. Stimulation of autologous CD3(+) T cells with leukemic DCs grown in the presence of various concentrations of autologous serum resulted in induction of more IFN-gamma-secreting cells than was the case for unprimed CD3(+) T cells. Leukemic DCs cultured with 10% autologous serum induced the highest numbers of IFN-gamma-secreting cells and CD8(+)CD56(+) T cells from autologous T cells. These results suggest that culture of AML blast cells in the presence of autologous serum could be used to generate leukemic DCs for immunotherapy against AML. The highest serum concentration appeared optimal for generating the most potent leukemic DCs.
急性髓系白血病(AML)免疫疗法的临床应用需要通过体外培养从AML原始细胞高效诱导树突状细胞(DC)。我们通过在含有GM-CSF、IL-4、TNF-α以及0%、2%、5%或10%人自体血清的AIM-V培养基中培养,研究了自体血清对AML患者白血病细胞来源的白血病DC特性的影响。在所有培养条件下,CD80、CD83、CD86和HLA-DR的表达均上调;然而,10%自体血清诱导了几种分子的最高表达水平。白血病DC刺激同种异体T细胞的能力随血清浓度增加而增强。用在不同浓度自体血清存在下培养的白血病DC刺激自体CD3(+) T细胞,与未致敏的CD3(+) T细胞相比,诱导产生了更多分泌IFN-γ的细胞。用10%自体血清培养的白血病DC从自体T细胞诱导产生的分泌IFN-γ的细胞和CD8(+)CD56(+) T细胞数量最多。这些结果表明,在自体血清存在下培养AML原始细胞可用于生成用于AML免疫治疗的白血病DC。最高血清浓度似乎最适合生成最有效的白血病DC。