Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab.
The effects of B-cell depletion with rituximab on regulatory T cells (Tregs) have not been determined. We investigated Tregs in patients receiving rituximab for chronic idiopathic thrombocytopenic purpura (ITP). The peripheral blood Tregs, identified as CD4+FOXP3+ T cells, were measured by flow cytometry prior to and after the immunotherapy. In addition, Tregs were analyzed for their usage of the T-cell receptor (TCR) beta-variable (VB) region gene as well as their regulatory function as assessed by cell proliferation assays. Pretreatment data revealed a reduced number and a defective suppressive capacity of Tregs in ITP patients compared with control individuals. In addition, Tregs showed a polyclonal spectratype. Patients, particularly responders, showed restored numbers of Tregs as well as a restored regulatory function upon treatment with rituximab. These results indicate that patients with active ITP have a defective T regulatory cell compartment that can be modulated by a B cell-targeted therapy.
Stasi
Roberto
R
Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Rome, Italy. roberto.stasi@uniroma2.it
Cooper
Nichola
N
Del Poeta
Giovanni
G
Stipa
Elisa
E
Laura Evangelista
Maria
M
Abruzzese
Elisabetta
E
Amadori
Sergio
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab