Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura.
Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25(hi) Tregs. We found a com-parable frequency of circulating CD4+CD25(hi)Foxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25(hi) cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP.
Yu
Jin
J
Laboratory of Complement Biology, New York Blood Center, New York, NY 10021, USA.
Heck
Susanne
S
Patel
Vivek
V
Levan
Jared
J
Yu
Yu
Y
Bussel
James B
JB
Yazdanbakhsh
Karina
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D007108:Immune Tolerance; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000209:etiology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors