Dhodapkar M V, Steinman R M, Sapp M, Desai H, Fossella C, Krasovsky J, Donahoe S M, Dunbar P R, Cerundolo V, Nixon D F, Bhardwaj N
Laboratory of Immunology and Cellular Physiology, General Clinical Research Center, and Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10021, USA.
J Clin Invest. 1999 Jul;104(2):173-80. doi: 10.1172/JCI6909.
Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.
树突状细胞（DCs）是强大的抗原呈递细胞，可在小鼠中启动保护性T细胞免疫。为了研究DCs在人类中的免疫原性，我们对9名健康受试者进行皮下注射，先注射自体单核细胞衍生的成熟DCs作为对照，4 - 6周后再注射用钥孔戚血蓝蛋白（KLH）、HLA - A0201阳性限制性流感基质肽（MP）和破伤风类毒素（TT）脉冲处理的DCs。另外4名受试者仅接受这些抗原，未注射DCs。注射未脉冲处理的DCs或单独注射抗原均未能引发免疫反应。在所有9名注射了KLH脉冲处理的DCs的受试者中均观察到CD4(+) T细胞对KLH的致敏，并且在6名注射了TT脉冲处理的DCs的受试者中有5名出现了TT特异性T细胞免疫的增强。早在注射后7天，在所有6名HLA - A0201阳性受试者中，注射抗原脉冲处理的DCs导致新鲜分离的MP特异性、分泌IFN - γ的CD8(+) T细胞增加了数倍。当在培养中增强T细胞时，DC疫苗接种后MHC四聚体结合细胞和细胞毒性T细胞有所增加。这些数据提供了DCs在人类中具有免疫原性的首个对照证据，并证明单次注射成熟DCs可迅速扩大T细胞免疫。
