Ikezawa Yuko, Nakazawa Masatoshi, Tamura Chizuru, Takahashi Kazuo, Minami Mutsuhiko, Ikezawa Zenro
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Japan.
J Dermatol Sci. 2005 Aug;39(2):105-12. doi: 10.1016/j.jdermsci.2005.02.002.
It is well known that cyclophosphamide (Cy) treatment before sensitization paradoxically enhances rather than suppresses contact hypersensitivity (CH) reactions. In fact, Cy-treated mice developed a significant (p < 0.05) increase of the CH reactions to 2,4,6-trinitro-1-chrolobenzene (TNCB) in comparison with untreated mice.
In order to examine whether the target cells of Cy in the immuno-augmentative effect are CD25(+) CD4(+) regulatory T cells or not, we investigated effect of Cy treatment on CD25(+) CD4(+) T cells.
We examined Cy-treated CD25(+) CD4(+) T cells by flow cytometer and by inhibition assay on proliferation of CD25(-) CD4(+) T cells.
Cy treatment remarkably reduced the number and percentage of CD25(+) CD4(+) T cells in the spleen and lymph nodes 3 and 5 days later. Moreover, CD25(+) CD4(+) T cells taken from the Cy-treated mice 3 days later showed the lower suppressive activity on proliferation of CD25(-) CD4(+) T cells, as compared to that from the untreated mice. Furthermore, transfer of CD25(+) CD4(+) T cells from untreated mice resulted in a significant decrease (p < 0.05) of the CH reactions enhanced by Cy treatment.
These results indicate that enhancement of the CH reactions to TNCB by Cy treatment is attributed to the decrease in the number, percentage and the function of CD25(+) CD4(+) regulatory T cells.
众所周知，致敏前使用环磷酰胺（Cy）进行治疗反而会增强而非抑制接触性超敏反应（CH）。事实上，与未处理的小鼠相比，经Cy处理的小鼠对2,4,6-三硝基-1-氯苯（TNCB）的CH反应显著增加（p < 0.05）。
为了研究Cy免疫增强作用的靶细胞是否为CD25(+) CD4(+)调节性T细胞，我们研究了Cy处理对CD25(+) CD4(+) T细胞的影响。
我们通过流式细胞仪以及对CD25(-) CD4(+) T细胞增殖的抑制试验来检测经Cy处理的CD25(+) CD4(+) T细胞。
Cy处理3天和5天后，脾脏和淋巴结中CD25(+) CD4(+) T细胞的数量和百分比显著减少。此外，与未处理小鼠的细胞相比，3天后从经Cy处理的小鼠中获取的CD25(+) CD4(+) T细胞对CD25(-) CD4(+) T细胞增殖的抑制活性较低。此外，从未处理小鼠转移CD25(+) CD4(+) T细胞会导致经Cy处理增强的CH反应显著降低（p < 0.05）。
这些结果表明，Cy处理增强对TNCB的CH反应归因于CD25(+) CD4(+)调节性T细胞数量、百分比和功能的减少。
