CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis.
Patients who are chronically infected with hepatitis C virus (HCV) often develop mixed cryoglobulinemia (MC), a B-cell proliferative disorder with polyclonal activation and autoantibody production. We investigated if MC is associated with a deficit of CD4(+)CD25(+) immunoregulatory T (Treg) cells, which have been shown to control autoimmunity. Because Treg cells express higher amounts of CD25 than activated CD4(+) T cells, we analyzed blood CD4(+)CD25(high) Treg cells in 69 untreated patients chronically infected with HCV. Treg cell frequency in patients without MC (8.8% +/- 2.3%) or with asymptomatic MC (7.4% +/- 2.1%) was comparable to that of healthy controls (7.9% +/- 1.3%). In contrast, it was significantly reduced in symptomatic MC patients (2.6% +/- 1.2%, P <.001) even when compared to a panel of untreated HCV(-) patients with different inflammatory disorders (6.2% +/- 0.8%, P <.0001). In symptomatic MC patients, the purified remaining CD4(+)CD25(+) T cells retained suppressive activity in vitro. These results, together with experimental data showing that depletion of Treg cells induces autoimmunity, suggest a major role of Treg cell deficiency in HCV-MC vasculitis and this is the first report of a quantitative Treg cell deficiency in virus-associated autoimmunity.
Boyer
Olivier
O
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, CNRS/UPMC, UMR 707 and Service de Médecine Interne, Hôpital Pitié-Salpêtrière, Paris, France.
Saadoun
David
D
Abriol
Julien
J
Dodille
Mélanie
M
Piette
Jean-Charles
JC
Cacoub
Patrice
P
Klatzmann
David
D
D000328:Adult; D000368:Aged; D015551:Autoimmunity; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D003449:Cryoglobulinemia / Q000209:etiology* / Q000276:immunology / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D015375:Receptors, Interleukin-2; D050378:T-Lymphocytes, Regulatory / Q000473:pathology / Q000821:virology; D014657:Vasculitis / Q000209:etiology / Q000276:immunology / Q000821:virology
D015375:Receptors, Interleukin-2