Cyclophosphamide decreases the number, percentage and the function of CD25 + CD4 + regulatory T cells, which suppress induction of contact hypersensitivity

Abstract

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.