OBJECTIVE: Rituximab is a therapeutic anti-CD20 antibody used for in vivo depletion of B cells in proliferative and autoimmune diseases. However, the mechanisms of action are not fully understood, since not all of the therapy-mediated effects can be explained by the depletion of antibody-secreting cells. In addition to B cells, there is also a small population of T cells coexpressing CD20 in all individuals. This study was conducted to examine the phenotype and function of CD3+CD20+ T cells in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: The phenotype and apoptosis of peripheral blood mononuclear cells from healthy donors and RA patients were examined by 4-color fluorescence-activated cell sorting analyses. Cytokine production was determined by intracellular staining and measurement of cytokines in the supernatants. Proliferation of sorted T cell populations was analyzed using 3H-thymidine uptake assays. RESULTS: In healthy individuals, 0.1-6.8% of peripheral blood T cells (mean 1.6%; n=142) coexpressed CD20, which was not significantly different from that in the peripheral blood of RA patients, in whom 0.4-2.6% of T cells (mean 1.2%; n=27) were CD20+. During rituximab therapy, the CD20+ T cells along with the B cells were eliminated from the RA peripheral blood. Among the CD20+ T cells, 45% coexpressed CD8 and 55% coexpressed CD4. Polyclonal CD3+CD20+ cells were functionally characterized by constitutive cytokine production (i.e., interleukin-1beta and tumor necrosis factor alpha), a low proliferative capacity, a high activation state, and enhanced susceptibility to apoptosis. CONCLUSION: These findings suggest that CD20+ T cells represent a terminally differentiated cell type with immune-regulatory and proinflammatory capacities. Depletion of CD20+ T cells may be an additional mechanism by which anti-CD20 therapy functions in patients with RA.
OBJECTIVE:Rituximab is a therapeutic anti-CD20 antibody used for in vivo depletion of B cells in proliferative and autoimmune diseases. However, the mechanisms of action are not fully understood, since not all of the therapy-mediated effects can be explained by the depletion of antibody-secreting cells. In addition to B cells, there is also a small population of T cells coexpressing CD20 in all individuals. This study was conducted to examine the phenotype and function of CD3+CD20+ T cells in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: The phenotype and apoptosis of peripheral blood mononuclear cells from healthy donors and RApatients were examined by 4-color fluorescence-activated cell sorting analyses. Cytokine production was determined by intracellular staining and measurement of cytokines in the supernatants. Proliferation of sorted T cell populations was analyzed using 3H-thymidine uptake assays. RESULTS: In healthy individuals, 0.1-6.8% of peripheral blood T cells (mean 1.6%; n=142) coexpressed CD20, which was not significantly different from that in the peripheral blood of RApatients, in whom 0.4-2.6% of T cells (mean 1.2%; n=27) were CD20+. During rituximab therapy, the CD20+ T cells along with the B cells were eliminated from the RA peripheral blood. Among the CD20+ T cells, 45% coexpressed CD8 and 55% coexpressed CD4. Polyclonal CD3+CD20+ cells were functionally characterized by constitutive cytokine production (i.e., interleukin-1beta and tumor necrosis factor alpha), a low proliferative capacity, a high activation state, and enhanced susceptibility to apoptosis. CONCLUSION: These findings suggest that CD20+ T cells represent a terminally differentiated cell type with immune-regulatory and proinflammatory capacities. Depletion of CD20+ T cells may be an additional mechanism by which anti-CD20 therapy functions in patients with RA.
Authors: H-Christian von Büdingen; Arumugam Palanichamy; Klaus Lehmann-Horn; Brady A Michel; Scott S Zamvil Journal: Eur Neurol Date: 2015-03-25 Impact factor: 1.710
Authors: Arumugam Palanichamy; Sarah Jahn; Dorothee Nickles; Mia Derstine; Aya Abounasr; Stephen L Hauser; Sergio E Baranzini; David Leppert; H-Christian von Büdingen Journal: J Immunol Date: 2014-06-13 Impact factor: 5.422
Authors: Tamás Kobezda; Sheida Ghassemi-Nejad; Katalin Mikecz; Tibor T Glant; Zoltán Szekanecz Journal: Nat Rev Rheumatol Date: 2014-01-07 Impact factor: 20.543
Authors: Andreas Kronbichler; Paul König; Martin Busch; Gunter Wolf; Gert Mayer; Michael Rudnicki Journal: Wien Klin Wochenschr Date: 2013-04-27 Impact factor: 1.704