GM-CSF production by CD4+ T cells in MS patients: regulation by regulatory T cells and vitamin D.
J Neuroimmunol
; 280: 36-42, 2015 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-25773153
ABSTRACT
BACKGROUND/OBJECTIVE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vitamin D
/
CD4-Positive T-Lymphocytes
/
Granulocyte-Macrophage Colony-Stimulating Factor
/
T-Lymphocytes, Regulatory
/
Multiple Sclerosis
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Neuroimmunol
Year:
2015
Document type:
Article