Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis

Chris L Ayers; Jason P Mendoza; Sushmita Sinha; Khrishen Cunnusamy; Benjamin M Greenberg; Elliot M Frohman; Nitin J Karandikar

doi:10.1016/j.clim.2013.02.015

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Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis

Journal article

Open access

Peer reviewed

Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis

Chris L Ayers, Jason P Mendoza, Sushmita Sinha, Khrishen Cunnusamy, Benjamin M Greenberg, Elliot M Frohman and Nitin J Karandikar

Clinical immunology (Orlando, Fla.), Vol.147(2), pp.105-119

05/2013

DOI: 10.1016/j.clim.2013.02.015

PMCID: PMC3634883

PMID: 23578552

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Abstract

Daily administration of FDA-approved glatiramer acetate (GA) has beneficial effects on clinical course of relapsing remitting multiple sclerosis (RRMS). Although mechanisms of GA-action have been widely investigated and partially understood, immediate immune dynamics following GA-therapy are unknown. In the present study, we characterized the immediate effects of GA on phenotype, quantity and function of immune cells in MS patients. Prominent changes in immune cells were detected within 4–12h post-first GA-injection. T-cell modulation included significantly decreased CD4/CD8 ratio, perturbed homeostasis of predominantly CD8+ T-cells, significant enhancement in CD8+ T-cell mediated suppression and inhibitory potential of induced CD4-suppressors. Changes in APC were restricted to monocytes and included reduced stimulatory capacity in MLR and significantly increased IL-10 and TNF-α production. Our study provides the first evidence that GA treatment induces rapid immunologic changes within hours of first dose. Interestingly, these responses are not only restricted to innate immune cells but also include complex modulation of T-cell functionality. •GA is active, in vivo, within 12h of administration.•GA induced early modulation of not only innate immune cell types but also T cell functionality.•GA restores inhibitory potential of induced suppressors very early during therapy initiation.•This study is a critical step toward developing better immunotherapeutic strategies.

Glatiramer acetate

Immunomodulation

Multiple sclerosis

Details

Title: Subtitle: Modulation of immune function occurs within hours of therapy initiation for multiple sclerosis
Creators: Chris L Ayers - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Jason P Mendoza - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Sushmita Sinha - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Khrishen Cunnusamy - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Benjamin M Greenberg - Department of Neurology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Elliot M Frohman - Department of Neurology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Nitin J Karandikar - Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA
Resource Type: Journal article
Publication Details: Clinical immunology (Orlando, Fla.), Vol.147(2), pp.105-119
DOI: 10.1016/j.clim.2013.02.015
PMID: 23578552
PMCID: PMC3634883
NLM abbreviation: Clin Immunol
ISSN: 1521-6616
eISSN: 1521-7035
Publisher: Elsevier Inc
Language: English
Date published: 05/2013
Academic Unit: Pathology
Record Identifier: 9984047977602771

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