http://neurology.medscape.com/Medscape/Neurology/AskExperts/MS/2001/09/NEUR-ae96.html

Question

What do you think about routinely assessing lymphocyte subpopulations in the peripheral blood of patients with multiple sclerosis (MS)? Is there an association between the activity of the disease and the number of CD3+, CD4+, and CD8+ cells in the peripheral blood? The chief of my department asks that all patients with MS undergo periodic measurement of all peripheral blood lymphocyte subpopulations, even when there are no clinical signs and symptoms of the disease. Is there a rationale for periodic (every 3 months) evaluations of peripheral blood lymphocyte subpopulations in patients under clinical observation for MS? Are CSF levels of these lymphocytes more relevant?

Response

from Mark Freedman, MD, 09/27/01

Lymphocyte subsets fluctuate even in healthy people with no underlying disease, and small changes in the overall pool of lymphocytes bearing certain phenotypic markers such as CD4 or CD8 are probably of little interest and benefit. There was a time when CD8+ cells in general were considered to be the immune T "suppressor" cells and hence the thought was that when they were low in number, there was a greater chance of relapse compared with when they were high. Over the years we have learned a lot about immune regulation and know now that identifying regulating cells would not be possible by simple phenotypic markers alone. Rather, it is the nature of what they do, such as release cytokine, when they encounter their antigen that indicates whether they are capable of immune regulation.
It might be useful to look at certain T cell subsets by assays examining cytokine production intracellularly especially in response to an antigen such as myelin basic protein. A shift away from Th1 to Th2 or Th3 type T cells could indicate a stable state of "regulation," whereas a shift to Th1 could indicate a tendency to disease activity. Similar studies have now been performed with patients taking immunomodulatory therapy such as glatiramer acetate or interferon-beta. These studies are of interest from a scientific basis but are extremely tedious and costly and therefore would not be useful for the routine monitoring of patients.

In summary, there is really no evidence to suggest that routine monitoring of CD3/CD4/CD8 lymphocyte subsets from either blood or CSF would be at all helpful in the management of MS.

Suggested Reading
 

• Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis: Principles, problems and perspectives. Brain. 1997;120:865-916.