Defective functions of circulating CD4+CD25+ and CD4+CD25- T cells in patients with chronic ordinary urticaria.
BACKGROUND
Patients with chronic ordinary urticaria (CU) are divided into two groups: 30-50% have chronic autoimmune urticaria, and the remainder have chronic idiopathic urticaria. CD4(+)CD25(+) regulatory T (Treg) cells play critical roles in maintaining peripheral tolerance and preventing autoimmunity, but the characteristics of Treg cells have not yet been defined in CU.


OBJECTIVE
To identify whether CD4(+) T cells play an important immunoregulatory role in the etiology of CU, we determined the frequencies and functions of circulating CD4(+)CD25(+) and CD4(+)CD25(-) T cells in CU patients and healthy control subjects, with special focus on the characteristics of CD4(+)CD25(+) T cells.


METHODS
Peripheral blood mononuclear cells (PBMCs) were obtained from CU and healthy controls in this study. The frequency of CD4(+)CD25(+) T cells in PBMCs was detected by flow cytometry. The expression levels of forkhead box P3 (FOXP3) and transforming growth factor-beta (TGF-beta) in CD4(+)CD25(+) T cells were detected by real-time PCR. Furthermore, the suppressive function of CD4(+)CD25(+) T cells was analyzed. Additionally, the Th1/Th2 cytokine secretory profile in mitogen-stimulated CD4(+)CD25(-) T cells was measured by ELISA.


RESULTS
An increased frequency of CD4(+)CD25(+) T cells was observed in CU patients (n=19) compared to control subjects (n=7). No significant difference was detected in the expression levels of FOXP3 or TGF-beta between CU patients (n=14) and control subjects (n=7). Strikingly, the suppressive capacity of CD4(+)CD25(+) Treg cells from 2 of 5 CU patients was partially defective. We also found that cytokine production from CD4(+)CD25(-) T cells was significantly reduced in CU patients (n=9) compared to healthy donors (n=11).


CONCLUSIONS
Our data demonstrate that CD4(+)CD25(+) and CD4(+)CD25(-) T cells in PBMCs exhibit defective functions in CU patients.
Chen
Wu-Charng
WC
Pediatrics, Cathay General Hospital, Taipei, Taiwan, ROC.
Chiang
Bor-Luen
BL
Liu
H Eugene
HE
Leu
Sy-Jye
SJ
Lee
Yueh-Lun
YL
D000293:Adolescent; D000328:Adult; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014581:Urticaria / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology*
D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta