GM-CSF production by CD4+ T cells in MS patients: Regulation by regulatory T cells and vitamin D

• Published in: Journal of neuroimmunology Vol. 280; pp. 36 - 42
• Main Authors: Peelen, E., Muris, A.-H., Damoiseaux, J., Knippenberg, S., Broens, K., Smolders, J., Cohen Tervaert, J.W., Hupperts, R., Thewissen, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2015
• Subjects: Adult; Allergy and Immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cytokines - metabolism; Female; Flow Cytometry; GM-CSF; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Humans; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - pathology; Neurology; Regulatory T cell; Statistics, Nonparametric; T helper cell; T-Lymphocytes, Regulatory - physiology; Time Factors; Vitamin D; Vitamin D - pharmacology; Young Adult; Multiple sclerosis; Vitamin D; GM-CSF; T helper cell; Regulatory T cell
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2015.02.007

Data from animal models of MS suggest that GM-CSF+CD4+T cells are pathogenic cells. Therefore, GM-CSF production by CD4+T cells of MS patients and their susceptibility to regulatory mechanisms were investigated. Intracellular flowcytometry was performed to determine the GM-CSF+CD4+T cell fraction in PBMC and CSF of MS patients and controls. The effect of regulatory T cells (Tregs) on GM-CSF production by CD4+T cells was studied in MS patients using a proliferation–suppression assay. Finally, GM-CSF+CD4+T cell fraction and GM-CSF protein levels in supernatant were assessed in anti-CD3-stimulated CD4+T cell cultures derived from healthy controls and MS patients, in the presence or absence of the active vitamin D metabolite calcitriol. The GM-CSF+CD4+T cell fraction in the peripheral blood did not differ between controls and MS patients. This T cell population could also be detected in the CSF of both subjects with MS as well as subjects with another diagnosis. In the CSF, it comprised a significant fraction of the T cell population. Upon in vitro stimulation of PBMC with anti-CD3 antibody, no differences were observed in GM-CSF+CD4+T cell frequencies. GM-CSF secretion was susceptible to regulation by Treg and vitamin D. Suppression of GM-CSF secretion by vitamin D was reduced in MS patients. Our study showed no elevation in GM-CSF+CD4+T cell fractions in MS patients compared to controls. Furthermore, GM-CSF secretion was prone to regulation by Treg and vitamin D, the latter being less effective in MS patients. •Peripheral GM-CSF+CD4+ T cell frequencies do not differ between MS patients and HC.•GM-CSF+CD4+ T cells are enriched in CSF compared to blood, though not MS-specific.•Activation induced CD4 T cell GM-CSF secretion is not different between MS and HC.•GM-CSF secretion by CD4 T cells is controlled by regulatory T cells and vitamin D.•Downregulation of Th GM-CSF secretion by vitamin D is less efficient in MS patients.