Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene.
T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes.
Vandenbark
A A
AA
Tykeson MS Research Laboratory, Neuroimmunology Research, VA Medical Center, Portland, OR 97207, USA. vandenba@ohsu.edu
Finn
T
T
Barnes
D
D
Culbertson
N
N
Chou
Y K
YK
Hicks
K
K
Bakke
A
A
Mass
M
M
Whitham
R
R
Offner
H
H
Bourdette
D
D
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003208:Concanavalin A / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014611:Vaccination
D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003208:Concanavalin A; D016753:Interleukin-10; D007371:Interferon-gamma