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


METHODS
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.


CONCLUSIONS
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.
Ikezawa
Yuko
Y
Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Japan.
Nakazawa
Masatoshi
M
Tamura
Chizuru
C
Takahashi
Kazuo
K
Minami
Mutsuhiko
M
Ikezawa
Zenro
Z
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D003520:Cyclophosphamide; D010853:Picryl Chloride