Local accumulation of FOXP3+ regulatory T cells: evidence for an immune evasion mechanism in patients with large condylomata acuminata.
Condylomata acuminata derived from the infection of human papillomavirus is a common sexually transmitted disease. Although T cell-mediated cellular immunity is considered as the main arm against such infection, the regulation of T cell immune responses in genital condylomata is unclear to date. In this study, we analyzed FOXP3(+) regulatory T cells in genital condylomata of patients. The results show that FOXP3(+) regulatory T cells with suppressive function accumulated in large warts. Consistently, the immunosuppressive milieu in large warts was characterized by high expression of IL-10 and TGF-beta1 and low expression of IL-2 and IFN-gamma. The responsiveness of wart-infiltrating T cells both in vitro and in vivo can be increased by depleting FOXP3(+) T cells. The accumulation of FOXP3(+) regulatory T cells in large warts can be partly ascribed to the chemotaxis of CCL17 and CCL22, derived from Langerhans cells and macrophages in wart. Although such accumulation favors the local immunosuppression, it seems not to influence the systemic immunity. In conclusion, these findings demonstrate that FOXP3(+) regulatory T cells play an important role in genital condylomata, which has multiple implications in the comprehensive treatment of condylomata acuminata.
Cao
Yuchun
Y
Department of Dermatology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Zhao
Jie
J
Lei
Zhang
Z
Shen
Shiqian
S
Liu
Cong
C
Li
Dong
D
Liu
Jihong
J
Shen
Guan-Xin
GX
Zhang
Gui-Mei
GM
Feng
Zuo-Hua
ZH
Huang
Bo
B
D002465:Cell Movement; D054414:Chemokine CCL17 / Q000096:biosynthesis / Q000276:immunology; D054422:Chemokine CCL22 / Q000096:biosynthesis / Q000276:immunology; D003218:Condylomata Acuminata / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D054398:Receptors, CCR4 / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D054398:Receptors, CCR4; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma