In article <30DE9342E2D at prl.pulmonary.ubc.ca> DANDERSON at PRL.PULMONARY.UBC.CA writes:
>>An immunization attempt would be interesting but I have
>a mechanistic question. Do these patients with zoster have a
>depressed cellular response in the face of a sufficient humoral
>response. Is the mechanism of this selective immunosuppression
>known??
As far as I know, the situation in zoster is not well understood
(as is the case with most viral pathogenesis questions, of course). The
related virus, herpes simplex virus, has been studied in more detail (and
I know more about it, note the cunning switch of fields). With HSV
reactivation, the virus seems to reactivate in spite of a perfectly
competent humoral immune response. There is often a *moderate*
suppression of the cellular immune response, concurrent with the
reactivation. The most probable explanation is that HSV takes advantage
of this suppression to show overt symptoms, but it is almost equally
possible that some of this immune suppression is actually mediated by the
virus itself. (The timing is not much help. Immune suppression is seen
before the clinical onset of cold sores, but a clinically apparent cold
sore represents probably millions of infected cells, so this may not tell
much about what's happening when the infection actually begins.
Furthermore, the cold sore may even represent the host response to the
virus, since there is an immune infiltrate at that time.)
I don't find the degree of immune suppression in HSV enough to really
account for reactivation; for one thing, the many other latent/persistent
viruses in everyone don't reactivate at the same time. Certainly,
someone who has recurrent cold sores is not at greater risk of, say,
Pneumocytis carnii pneumonia or the other hallmarks of immune
deficiency. HSV does have a pretty potent spectrum of immune evasion
mechanisms; zoster probably does as well (because every herpes virus
that's been examined in detail does), although not all the ones in HSV
are reflected in VZV.
On the third, or fourth, hand, people who have suppressed cellular
immunity do have problems with recurrent herpes infections, including
HSV, cytomegalovirus (in AIDS patients, for example), EBV (transplant
patients eg) and VZV. So, to summarize the above, it seems very likely
that humoral immunity is not enough to keep a herpes virus under
control. This is not very surprising, of course, because these are the
paradigms of intracellular viruses, so antibody has little chance to
impact on them. (This says nothing about the ability of antibody to
*prevent and initial infection*, as in vaccines; there you're starting
with extracellular virus.) "Selective immunosuppression of cellular
immune response" is probably not strictly correct - I prefer phrases like
"immune evasion" - but to an approximation it reflects the situation.
References and reviews for the above statements available on request.
Ian
--
Ian York (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921 Fax (617)-632-2627
