Faculty Opinions recommendation of Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab.

2016 ◽  
Author(s):  
Moin Saleem
Keyword(s):  
T Cell ◽  
B Cell ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Regulatory T Cell ◽  
Thrombocytopenic Purpura ◽  
Cell Changes

Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell–depleting therapy with rituximab

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1147-1150 ◽  
Author(s):  
Roberto Stasi ◽  
Nichola Cooper ◽  
Giovanni Del Poeta ◽  
Elisa Stipa ◽  
Maria Laura Evangelista ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Cell Receptor ◽  
Regulatory Function ◽  
T Regulatory Cell ◽  
Region Gene ◽  
Thrombocytopenic Purpura ◽  
Cell Changes

Abstract 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) β-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.

scholarly journals Depressed functional and phenotypic properties of T but not B lymphocytes in idiopathic thrombocytopenic purpura

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1455-1460 ◽  
Author(s):  
R Mylvaganam ◽  
RO Garcia ◽  
YS Ahn ◽  
PG Sprinz ◽  
CI Kim ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
B Lymphocytes ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Cellular Immunity ◽  
T Cell Subsets ◽  
Phenotypic Properties ◽  
Thrombocytopenic Purpura ◽  
Cell Mitogen ◽  
Normal Controls

Abstract Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which the abnormality in cellular immunity has remained only vaguely defined. Previously we have shown that patients with ITP in its active phase have abnormal T cell subsets. We then examined the phenotypes of T and B lymphocytes in an additional 28 patients with ITP and 32 age- and sex-matched normal controls and compared the lymphocytes' capacity to respond to polyclonal T, T cell-dependent B, and B cell mitogens. Blastogenesis to optimal (5.0 micrograms/mL) and suboptimal (0.5 microgram/mL) concentrations of the polyclonal T cell mitogens were markedly depressed in patients compared with normal controls (P less than .0005). Similarly, a severe depression in response was noted with the polyclonal T cell-dependent B cell mitogen (P less than .000001). No difference was seen, however, with the polyclonal B cell mitogen. The proportions of pan-T and T helper/inducer lymphocytes were significantly depressed (P less than .005 and P less than .000005 respectively), and the T suppressor/cytotoxic lymphocytes increased (P less than .02) in patients relative to controls. But there was no difference in the proportion of B lymphocytes or in their functional response. The abnormal cellular immunity appears to be due to a defect in the T lymphocyte population without involvement of the B lymphocytes.

scholarly journals Depressed functional and phenotypic properties of T but not B lymphocytes in idiopathic thrombocytopenic purpura

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1455-1460
Author(s):  
R Mylvaganam ◽  
RO Garcia ◽  
YS Ahn ◽  
PG Sprinz ◽  
CI Kim ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
B Lymphocytes ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Cellular Immunity ◽  
T Cell Subsets ◽  
Phenotypic Properties ◽  
Thrombocytopenic Purpura ◽  
Cell Mitogen ◽  
Normal Controls

Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which the abnormality in cellular immunity has remained only vaguely defined. Previously we have shown that patients with ITP in its active phase have abnormal T cell subsets. We then examined the phenotypes of T and B lymphocytes in an additional 28 patients with ITP and 32 age- and sex-matched normal controls and compared the lymphocytes' capacity to respond to polyclonal T, T cell-dependent B, and B cell mitogens. Blastogenesis to optimal (5.0 micrograms/mL) and suboptimal (0.5 microgram/mL) concentrations of the polyclonal T cell mitogens were markedly depressed in patients compared with normal controls (P less than .0005). Similarly, a severe depression in response was noted with the polyclonal T cell-dependent B cell mitogen (P less than .000001). No difference was seen, however, with the polyclonal B cell mitogen. The proportions of pan-T and T helper/inducer lymphocytes were significantly depressed (P less than .005 and P less than .000005 respectively), and the T suppressor/cytotoxic lymphocytes increased (P less than .02) in patients relative to controls. But there was no difference in the proportion of B lymphocytes or in their functional response. The abnormal cellular immunity appears to be due to a defect in the T lymphocyte population without involvement of the B lymphocytes.

Response to B-cell–depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2924-2930 ◽  
Author(s):  
Roberto Stasi ◽  
Giovanni Del Poeta ◽  
Elisa Stipa ◽  
Maria Laura Evangelista ◽  
Margherita M. Trawinska ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Fas Ligand ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
Control Group ◽  
Region Gene ◽  
Thrombocytopenic Purpura

AbstractRituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as idiopathic thrombocytopenic purpura (ITP). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of different peripheral blood T-cell subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR) β-variable (VB) region gene usage of CD4+ and CD8+ T-cell subpopulations following rituximab therapy. The study involved 30 patients with chronic ITP who received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared with the control group, pretreatment abnormalities of T cells in ITP patients included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P < .001), increased expression of Fas ligand on Th1 and Th2 cells (P < .001), increased expression of Bcl-2 mRNA (P = .003) and decreased expression of bax mRNA (P = .025) in Th cells, and expansion of oligoclonal T cells with no preferential use of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and 6 months after treatment, whereas they remained unchanged in nonresponders. Our findings indicate that in patients with ITP, response to B-cell depletion induced by rituximab is associated with significant changes of the T-cell compartment.

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

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