Nakai Noriaki, Katoh Norito, Kitagawa Tomoko, Ueda Eiichiro, Takenaka Hideya, Kishimoto Saburo
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
J Dermatol Sci. 2009 Apr;54(1):31-7. doi: 10.1016/j.jdermsci.2008.11.007. Epub 2009 Jan 20.
Regulatory T cells (Treg) may inhibit monocyte-derived melanoma antigen-pulsed dendritic cells (DC) vaccination in treatment of melanoma. However, the Treg level in peripheral blood mononuclear cells (PBMCs) following DC vaccination has not been examined in melanoma patients in Japan.
To evaluate differences in the helper T cell and Treg population and mRNA levels of Treg in pre- and post-DC vaccination PBMCs obtained from melanoma patients.
Levels of intracellular forkhead box protein 3 (Foxp3) mRNA as well as levels of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(+) T cells were examined by real-time PCR and flow cytometry using PBMCs from 9 patients who received DC vaccination.
Eight of the 9 cases and 7 of the 9 cases showed increased populations of CD4(+)CD25(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells, respectively after repeated DC vaccination. Five of 8 cases showed an increase of Foxp3 mRNA after treatment. Four of these 5 cases also had increased CD4(+)CD25(+) and CD4(+)CD25(+)Foxp3(+) T cells, but the fifth case showed a decrease in CD4(+)CD25(+)Foxp3(+) T cells. Three cases showed a decrease of Foxp3 mRNA. One of these 3 cases showed decreased population of CD4(+)CD25(+)Foxp3(+) T cells, but two cases showed increased population of CD4(+)CD25(+)Foxp3(+) T cells. In 3 of 8 cases Foxp3 expression at the cellular (protein) and mRNA level were inconsistent.
Repeated DC vaccination may commonly induce Treg and helper T cells at the cellular level. However, there are a few discrepancies of Treg expression at cellular and mRNA level.
调节性T细胞(Treg)可能会抑制单核细胞衍生的黑色素瘤抗原脉冲树突状细胞(DC)疫苗接种在黑色素瘤治疗中的效果。然而,日本黑色素瘤患者在DC疫苗接种后外周血单核细胞(PBMC)中的Treg水平尚未得到检测。
评估黑色素瘤患者接种DC疫苗前后PBMC中辅助性T细胞和Treg群体以及Treg的mRNA水平的差异。
使用来自9名接受DC疫苗接种患者的PBMC,通过实时PCR和流式细胞术检测细胞内叉头框蛋白3(Foxp3)mRNA水平以及CD4(+)CD25(+)Foxp3(+)和CD4(+)CD25(+) T细胞水平。
9例中的8例和9例中的7例在重复DC疫苗接种后分别显示CD4(+)CD25(+) T细胞和CD4(+)CD25(+)Foxp3(+) T细胞群体增加。8例中的5例在治疗后显示Foxp3 mRNA增加。这5例中的4例CD4(+)CD25(+)和CD4(+)CD25(+)Foxp3(+) T细胞也增加,但第5例CD4(+)CD25(+)Foxp3(+) T细胞减少。3例显示Foxp3 mRNA减少。这3例中的1例显示CD4(+)CD25(+)Foxp3(+) T细胞群体减少,但2例显示CD4(+)CD25(+)Foxp3(+) T细胞群体增加。8例中的3例在细胞(蛋白质)和mRNA水平上的Foxp3表达不一致。
重复DC疫苗接种通常可能在细胞水平上诱导Treg和辅助性T细胞。然而,在细胞和mRNA水平上Treg表达存在一些差异。