Eﬀect of gender on T-cell proliferative responses to myelin
proteolipid protein antigens in patients with multiple sclerosis and
Judith M. Greer*, Peter A. Csurhes, Michael P. Pender, Pamela A. McCombe
Neuroimmunology Research Centre, School of Medicine, The University of Queensland, Australia
Received 4 December 2003; revised 25 February 2004; accepted 1 March 2004
Multiple sclerosis (MS) is an inﬂammatory demyelinating disorder of the central nervous system. Gender inﬂuences both
susceptibility to MS, with the disease being more common in women, and the clinical course of disease, with an increased proportion
of males developing the primary progressive form of the disease. The basis for these diﬀerences may include genetic and
immunological factors, and the immunological diﬀerences between men and women may be inﬂuenced by the eﬀects of the sex
hormones. Over several years we have collected blood from MS patients and controls, and measured T-cell responses to myelin
proteolipid protein (PLP) and myelin basic protein (MBP) and have shown increased responses to PLP in MS patients compared
to healthy controls and patients with other neurological diseases. In the present study we analyzed data from over 500 individuals,
to determine whether there are diﬀerences between males and females in their responses to PLP and MBP. We found that there was
higher frequency of increased T-cell reactivity to immunodominant PLP peptides in women than in men, particularly in non-MS
individuals. We suggest that this may be relevant to the higher prevalence of MS in women.
2004 Elsevier Ltd. All rights reserved.
Many studies have shown that potentially auto-
reactive T and B cells can be found in the blood of
healthy individuals [1–9]. It is thought that these cells are
kept in check by peripheral tolerance mechanisms, and
that people who are susceptible to autoimmunity might
have defects in these tolerance mechanisms, allowing the
activation of the autoreactive cells and the develop-
ment of pathogenic autoreactivity [10–14]. Autoreactive
T cells and antibodies directed against central nervous
system (CNS) antigens, particularly the components of
myelin or oligodendrocytes [15–17], have been impli-
cated in the pathogenesis of multiple sclerosis (MS), a
relatively common disorder causing signiﬁcant neuro-
logical disability . MS frequently aﬀects young adults
causing diverse neurological symptoms and signs includ-
ing visual impairment, weakness and numbness, loss of
balance and bladder disturbance .
We and others have found signiﬁcantly increased
T-cell reactivity to myelin proteolipid protein (PLP)
[5,20–23] in patients with MS compared to controls and
compared to patients with other neurological disorders.
In addition, we have shown that surges in the frequency
of circulating T cells speciﬁc for PLP correlates with
inﬂammatory CNS disease activity assessed by magnetic
resonance imaging (MRI) in some MS patients .
There are also reports of increased T-cell reactivity to
myelin basic protein (MBP) [24–26], although we and
others have not been able to conﬁrm this [9,20,27,28],
and to myelin oligodendrocyte glycoprotein (MOG)
. We and others have also found increased T- or
B-cell reactivity to gangliosides [29–32].
It is generally found that MS is more prevalent in
females than in males, with a ratio of approximately
2:1. Our studies have been carried out in Queensland,
* Corresponding author. Department of Medicine, Clinical
Sciences Building, Royal Brisbane Hospital, Herston QLD 4029,
Australia. Tel.: +61-7-3365-5133; fax: +61-7-3365-5462
E-mail address: email@example.com (J.M. Greer).
Journal of Autoimmunity 22 (2004) 345–352
0896-8411/04/$ - see front matter 2004 Elsevier Ltd. All rights reserved.