Abstract:
:Regulatory T cells (Tregs) play a fundamental role in the maintenance of self-tolerance and immune homeostasis. Defects in Treg function and/or frequencies have been reported in multiple disease models. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Compelling evidence supports a neuroprotective role for Tregs in this disease. Indeed, rapid progression in ALS patients is associated with decreased FoxP3 expression and Treg frequencies. Thus, we propose that strategies to restore Treg number and function may slow disease progression in ALS. In this study, we developed a robust, Good Manufacturing Practice (GMP)-compliant procedure to enrich and expand Tregs from ALS patients. Tregs isolated from these patients were phenotypically similar to those from healthy individuals but were impaired in their ability to suppress T-cell effector function. In vitro expansion of Tregs for 4 weeks in the presence of GMP-grade anti-CD3/CD28 beads, interleukin (IL)-2 and rapamcyin resulted in a 25- to 200-fold increase in their number and restored their immunoregulatory activity. Collectively, our data facilitate and support the implementation of clinical trials of adoptive therapy with ex vivo expanded and highly suppressive Tregs in patients with ALS.
journal_name
Cytotherapyjournal_title
Cytotherapyauthors
Alsuliman A,Appel SH,Beers DR,Basar R,Shaim H,Kaur I,Zulovich J,Yvon E,Muftuoglu M,Imahashi N,Kondo K,Liu E,Shpall EJ,Rezvani Kdoi
10.1016/j.jcyt.2016.06.012subject
Has Abstractpub_date
2016-10-01 00:00:00pages
1312-24issue
10eissn
1465-3249issn
1477-2566pii
S1465-3249(16)30439-Xjournal_volume
18pub_type
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