You make an interesting suggestion, however if you could further elaborate
then this could be helpful in fully understanding what you are implying. For
instance, you say that 'T cells could differentiate without the peripheral
[lymphatic system]', but then go on to say there is 'no evidence of T cell
apoptosis within the synovial fluid [of joints]', what do you mean?
Remember, in theory all that is needed to activate a T cell is the binding
of a specific antigen to its TCR-CD3 complex after being presented by MHC
class I (all nucleated cells) cells or MHC class II antigen presenting cells
(APCs) along with co-stimulatory binding (i.e. B7 1, 2 receptors, CD46
etc.). T cell induced apoptosis in the absence of co-stimulatory binding is
still something of a mystery, for example read about superantigen
activation - is this what you meant when discussing apoptosis?
Also, in a subset of MS patients, reactive T cells to MBP and MOG are
found, and through animal experimental studies (i.e. experimental allergic
encephalomyelitis or EAE) immunodominant regions of MBP have been
determined. This would still therefore imply that neural antigens were
somehow leaving the CNS and entering the lymphatic system. This is perhaps
where those favouring molecular mimicry would step in and say that certain
viruses etc., may carry such immunodominant regions that activate the
subset MBP reactive T cell population giving rise to MS. In addition, keep
in mind that really, only activated T cells can pass through the BBB and
enter the CNS, since the activation state of the T cell (and of the CNS
vessels) are at least additive in their effect on the number of entering T
cells.
The paradox still remains - how does neural antigen activate T cells in
vivo?
Andrew Slater <aji at ntlworld.com> wrote in message
news:38FF2A93.20B785C3 at ntlworld.com...
> It is a very interesting question. And one that also applies in the case
of
> Rheumatoid arthritis. The synovial membrane and the various other sections
in
> the joints do not contain lymphatic vessels, but yet the activation of
naive
> T-cells occur.
>> A friend of mine offered what appeared to be a stupid idea, but now I
don't
> know. What if the activation of naive T-cells could differentiate outwith
the
> peripheral lymphatics, it is known that there is no evidence of T-cell
> apoptosis within the synovial fluid, thus the joints appear to be a
special
> case.
>> The mechanism may have evolved over the need to protect against pathogens
whose
> antigens do not cross such barriers as the blood brain barrier, Thus the
only
> way to initiate an immune response would be the local activation of naive
> T-cells perhaps through antigen presentation by tissue macrophages.
>> Anyone else have any ideas or even specialist knowledge in this field?
>> Theophilus Samuels wrote:
>> > At present is is thought that T cell activation (in response to neural
> > antigens such as MBP) occurs in the periphery, lymph nodes etc, which
then
> > allows them to penetrate the BBB and produce the crippling CNS
inflammatory
> > response observed in MS patients. I ask the following question - how
does
> > the neural antigen get into the peripheral lymphatic system in the first
> > place, since lymphatic vessels are not present in the CNS?
> >
> > T.L.S.
>
