Increase in circulating CD4+CD25+Foxp3+ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2170-2173 ◽  
Author(s):  
Caroline Hasselbalch Riley ◽  
Morten Krogh Jensen ◽  
Marie Klinge Brimnes ◽  
Hans Carl Hasselbalch ◽  
Ole Weis Bjerrum ◽  
...  

Abstract Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these patients. Foxp3+ regulatory T cells play a pivotal role in maintaining immune homeostasis and, importantly, preventing immune reactivity to self-antigens; however, their suppressive activity can compromise an effective antitumor immune response, and high frequencies of regulatory T cells in peripheral blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4+CD25+Foxp3+ T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN-α2 (13.0%; 95% confidence interval [CI] 10.8% to 15.2%) compared with healthy donors (6.1%; 95% CI 4.9% to 7.2%), patients with untreated chronic myeloproliferative neoplasms (6.9%; 95% CI 5.8% to 7.4%), or patients treated with hydroxyurea (5.8%; 95% CI 4.3% to 7.4%; P < .0001).

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  

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.


1986 ◽  
Vol 9 (5) ◽  
pp. 301-304 ◽  
Author(s):  
S. Stefoni ◽  
A. Nanni Costa ◽  
G. Liviano D'Arcangelo ◽  
M. Biavati ◽  
S. lannelli ◽  
...  

Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.


2000 ◽  
Vol 279 (3) ◽  
pp. H1434-H1439 ◽  
Author(s):  
Steffen-Sebastian Bolz ◽  
Susanne Pieperhoff ◽  
Cor De Wit ◽  
Ulrich Pohl

Long-term culture of resistance vessels allows introduction of molecular biology techniques for use in microvascular research. The aim of the present study was to establish a culture protocol that preserved vascular integrity and function in microvessels for 48 h in culture. Skeletal muscle resistance arteries were excised from the hamster gracilis muscle. Segments were assigned to immediate functional tests or to vessel culture, during which segments were perfused and superfused at a transmural pressure of 45 mmHg with Leibovitz (L15) medium containing 15% fetal calf serum and antibiotics for 48 h. Cultured and freshly isolated vessels showed similar levels of spontaneous tone, myogenic responses, changes in smooth muscle intracellular calcium (Cai 2+) (fura 2), and vascular diameter (video microscopy) in response to 0.3 M norepinephrine and similar concentration-response curves for acetylcholine (endothelium dependent, ± N ω-nitro-l-arginine) and sodium nitroprusside (endothelium independent). Measurements of endothelial Cai 2+ revealed similar acetylcholine-induced increases in endothelial Cai 2+ in both groups. It is concluded that vascular function can be preserved while maintaining vessels in culture. Thus it is possible to utilize protocols that require long-term treatment.


2010 ◽  
Vol 2010 ◽  
pp. 1-9
Author(s):  
U. Protzer ◽  
H. Abken

More than 350 million people worldwide are persistently infected with human heptatitis B virus (HBV) and at risk to develop liver cirrhosis and hepatocellular carcinoma making long-term treatment necessary. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Recent efforts in adoptive cell therapy are experimentally exploring immunotherapeutic elimination of HBV-infected cells by means of a biological attack with genetically engineered “designer” T cells.


2005 ◽  
Vol 167 (1-2) ◽  
pp. 175-182 ◽  
Author(s):  
Merja Soilu-Hänninen ◽  
Mikko Laaksonen ◽  
Arno Hänninen ◽  
Juha-Pekka Erälinna ◽  
Martin Panelius

2017 ◽  
Vol 37 (3) ◽  
pp. 1367-1378 ◽  
Author(s):  
Florencia Paula Madorsky Rowdo ◽  
Antonela Barón ◽  
Erika María Von Euw ◽  
José Mordoh

2014 ◽  
Vol 8 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Federico Serana ◽  
Marco Chiarini ◽  
Eugenia Quiros-Roldan ◽  
Daria Gotti ◽  
Cinzia Zanotti ◽  
...  

Naïve, central- and effector-like memory regulatory T cells (Tregs) were evaluated in untreated and long-term antiretroviral-treated HIV+ patients that showed comparable CD4+ cell levels, while being, respectively, viremic and aviremic. In the untreated patients, the percentage of naïve-like Tregs was significantly increased to the detriment of central memory regulatory T cells. This redistribution of regulatory Treg subsets may contribute to explain the partially preserved CD4+ cell counts seen in these patients despite the ongoing viremia. On the contrary, in the long-term treated patients, the percentages of Treg subsets were similar to those of healthy donors, demonstrating a restored Treg homeostasis. The characterization of Treg subsets, rather than an evaluation of the total Treg population, may lead to a deeper understanding of the Treg role in HIV infection and therapy.


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