TY - JOUR
T1 - T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls
AU - Hellings, Niels
AU - Baree, Mark
AU - Verhoeven, Christof
AU - D'hooghe, Marie Beatrijs
AU - Medaer, Robert
AU - Bernard, Claude Charles Andre
AU - Raus, Jef
AU - Stinissen, Piet
PY - 2001
Y1 - 2001
N2 - Myelin proteins, including myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) are candidate autoantigens in MS. It is not clear whether MS patients show a predominant reactivity to one or several myelin antigens. We evaluated the IFN-gamma production induced by MBP and MOG and selected MBP-, MOG- and PLP-peptides in MS patients and healthy controls using the IFN-gamma ELISPOT assay. Most MS patients and healthy controls showed a heterogeneous anti-myelin T-cell reactivity. Interestingly in MS patients a positive correlation was found between the anti-MOG and anti-MBP T-cell responses. No myelin peptide was preferentially recognized among the peptides tested (MBP 84-102, 143-168, MOG 1-22, 34-56, 64-86, 74-96, PLP 41-58, 184-199, 190-209). In addition the frequency of IL2R+ MBP reactive T-cells was significantly increased in blood of MS patients as compared with healthy subjects, indicating that MBP reactive T-cells exist in an in vivo activated state in MS patients. Most of the anti-MBP T-cells were of the Th1-type because reactivity was observed in IFN-gamma but not in IL-4 ELISPOT-assays. Using Th1 (IL-12) and Th2 (IL-4) promoting conditions we observed that the cytokine secretion pattern of anti-MBP T-cells still is susceptible to alteration. Our data further indicate that precursor frequency analysis of myelin reactive T-cells by proliferation-based assays may underestimate the true frequency of myelin specific T-cells significantly.
AB - Myelin proteins, including myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) are candidate autoantigens in MS. It is not clear whether MS patients show a predominant reactivity to one or several myelin antigens. We evaluated the IFN-gamma production induced by MBP and MOG and selected MBP-, MOG- and PLP-peptides in MS patients and healthy controls using the IFN-gamma ELISPOT assay. Most MS patients and healthy controls showed a heterogeneous anti-myelin T-cell reactivity. Interestingly in MS patients a positive correlation was found between the anti-MOG and anti-MBP T-cell responses. No myelin peptide was preferentially recognized among the peptides tested (MBP 84-102, 143-168, MOG 1-22, 34-56, 64-86, 74-96, PLP 41-58, 184-199, 190-209). In addition the frequency of IL2R+ MBP reactive T-cells was significantly increased in blood of MS patients as compared with healthy subjects, indicating that MBP reactive T-cells exist in an in vivo activated state in MS patients. Most of the anti-MBP T-cells were of the Th1-type because reactivity was observed in IFN-gamma but not in IL-4 ELISPOT-assays. Using Th1 (IL-12) and Th2 (IL-4) promoting conditions we observed that the cytokine secretion pattern of anti-MBP T-cells still is susceptible to alteration. Our data further indicate that precursor frequency analysis of myelin reactive T-cells by proliferation-based assays may underestimate the true frequency of myelin specific T-cells significantly.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11170179
M3 - Article
SN - 0360-4012
VL - 63
SP - 290
EP - 302
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 3
ER -