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variable gene usage in
cerebrospinal fluid lymphocytes in acute optic neuritis
a Neuroimmunology
Unit, Department of Immunology, Westmead Hospital, and Department of
Medicine, University of Sydney, Sydney, NSW, Australia, b Department of Molecular Genetics, The New
Children's Hospital, Westmead, NSW, Australia, c School of Science, University of Western Sydney
(Nepean), Parramatta, NSW, Australia
Correspondence to: Associate Professor GJ Stewart, Neuroimmunology Unit, Department of Immunology, Westmead Hospital, Westmead, NSW, 2145 Australia.
Received 1 December
1998 and in revised form 20 May 1999;
Accepted 28 May
1999
OBJECTIVES
There have
been many studies reporting restricted patterns of T cell receptor
usage in established multiple sclerosis and these have led to clinical
trials of immunomodulation directed at deleting clonal T cell
populations. The present study aims to test the hypothesis that highly
restricted T cell populations are also present in the CSF in the
earliest clinical stages of acute demyelinating disease of the CNS.
METHODST cell
receptor V
(TCRBV) gene expression was studied in CSF and blood in
nine patients with acute optic neuritis within 7 days of onset of
symptoms, six patients with an acute relapse of multiple sclerosis, and
13 control subjects. RNA was extracted and cDNA synthesised from
unstimulated CSF and blood lymphocytes, and TCRBV gene segments were
amplified from the cDNA by polymerase chain reaction (PCR) using 21 family specific primers. PCR products were separated by polyacrylamide
gel electrophoresis and detected via a labelled oligonucleotide probe.
A semiquantitative analysis of band intensity was performed by laser densitometry.
RESULTSTCRBV mRNA was
detected in the CSF of eight of nine patients with optic neuritis, six
of six patients with multiple sclerosis, and five of 13 controls, and
was closely correlated with the presence of oligoclonal IgG. Usage of a
single TCRBV family was demonstrated in two of nine patients with optic
neuritis and two of six patients with multiple sclerosis. The number of
TCRBV families expressed in the other patients ranged between 5 and 15 (optic neuritis) and 4 and 17 (multiple sclerosis).
CONCLUSIONSThere is a
relative lack of restriction of TCRBV usage by CSF lymphocytes in the
very earliest stages (<7 days) of acute optic neuritis. This may imply
either that multiple sclerosis is not a monoclonal disease even at
onset, or that the autoimmune response has widened before the disease
becomes clinically evident. This may have important consequences for
the design of immune therapies in multiple sclerosis. Further studies
are required to determine whether the CSF T cell repertoire at
presentation has prognostic importance. Longitudinal studies are
required to follow the CSF T cell repertoire from the time of
presentation and to determine whether it may have prognostic significance.
This article has been cited by other articles:
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  D Gestri, L Baldacci, R Taiuti, E Galli, E Maggi, M-P Piccinni, M Vergelli, and L Massacesi Oligoclonal T cell repertoire in cerebrospinal fluid of patients with inflammatory diseases of the nervous system J. Neurol. Neurosurg. Psychiatry, June 1, 2001; 70(6): 767 - 772. [Abstract] [Full Text] [PDF]
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