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

J Dermatol Sci. 2005 Aug;39(2):105-12. doi: 10.1016/j.jdermsci.2005.02.002.


Background: 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.

Objective: 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.

Method: We examined Cy-treated CD25(+) CD4(+) T cells by flow cytometer and by inhibition assay on proliferation of CD25(-) CD4(+) T cells.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cyclophosphamide / pharmacology*
  • Dermatitis, Contact / immunology*
  • Female
  • Flow Cytometry
  • Immunosuppressive Agents / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Picryl Chloride
  • Receptors, Interleukin-2 / biosynthesis*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Time Factors


  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Cyclophosphamide
  • Picryl Chloride