Brain, Vol 120, Issue 8 1437-1445, Copyright © 1997 by Oxford University Press
S Schmidt, C Linington, F Zipp, S Sotgiu, R de Waal Malefyt, H Wekerle and R Hohlfeld
The adoptive transfer of autoreactive S100 beta-specific T cells induces
experimental autoimmune panencephalomyelitis and uveoretinitis in the Lewis
rat, mimicking the distribution of lesions seen in a subset of patients
with multiple sclerosis. We studied the frequency and functional properties
of the human T-cell response to S100 beta in eight patients (two
relapsing-remitting multiple sclerosis, one chronic- progressive multiple
sclerosis, two with multiple sclerosis and uveitis, two neuromyelitis
optica, one panuveitis) and in seven healthy individuals, using bovine S100
beta for T-cell stimulation. Both in patients and controls, the frequency
of S100 beta-specific T-cell responses was half of that obtained for myelin
basic protein (MBP), and only 10% of that obtained using purified protein
derivative (PPD). The stimulation indices obtained in response to S100 beta
were also less than half those obtained with either MBP or PPD. However,
four long- term S100 beta-specific T-cell lines were established and
studied in more detail. The four T-cell lines all exhibited a CD4+, CD8-,
T-cell receptor alpha beta + surface phenotype and secreted tumour necrosis
factor-alpha, interferon-gamma, interleukin-10 and interleukin-4 upon
antigenic stimulation, but they were heterogenous with respect to T- cell
receptor usage; two T-cell lines expressed V beta 2, one V beta 6.7 and one
V beta 13. Antigen-specificity was confirmed using bovine S100 beta beta
and alpha beta-isoforms, as well as a recombinant rat S100 beta
preparation. The response to S100 beta was shown to the HLA- (human
leukocyte antigen-) DR-restricted for two of the S100 beta- specific T-cell
lines. Human S100 beta-specific T-cell lines were cytotoxic, although to a
lesser extent than MBP-specific T-cell lines derived from the same donors.
The phenotypic and functional properties of human S100 beta-specific T-cell
lines raise the possibility that these T cells are pathogenic, as they are
in the rat. The low frequency and proliferative index of S100
beta-specific, as opposed to MBP- specific T-cell responses suggests that
the T-cell response to this widely expressed calcium-binding protein is
under more efficient regulatory control.
ARTICLES
Multiple sclerosis: comparison of the human T-cell response to S100 beta and myelin basic protein reveals parallels to rat experimental autoimmune panencephalitis
Department of Neuroimmunology, Max-Planck Institute, Martinsried, Germany.
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