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The regeneration of CD4+ cells seems to be dependant on a thymic pathway as well as peripheral expansion of mature CD4+ cells.
Age-associated thymic involution restricts the thymic pathway and may be responsible for prolonged depletion in older children and adults.
The recovery ofCD4+ cells has been shown to be inversely correlated to age.

CVfactor wrote:Gerorge,

Yes, from what I read the thymus would at some point stop functioning all together. So in my mind I think HSCT should be viewed as a once in a lifetime procedure at middle age because of the length of time it takes for immune reconstruction.

In the last few weeks, I have begun to experience Lhermitte's sign which I never had before. I think maybe HSCT will be in my future if I continue to decline, but I think I will choose the myeoblative method.

Multiple sclerosis (MS) is a complex immune-mediated disorder of the CNS, which results from a combination of
genetic and environmental factors and their interactions [1]. Although genomewide association studies have discovered
numerous genetic variants predisposing to MS, the environment exerts a greater influence on susceptibility [2]. That
nurture is fundamental in MS has been known for decades. Monozygotic twins are, at most, 30% concordant, and familial MS risk is
significantly influenced by location and season of birth and the childhood environment [1,2]. Growing evidence lends strong
support to vitamin D deficiency and Epstein–Barr virus (EBV) infection as being key environmental risk factors.

CVfactor wrote:In my mind I believe MS is like a demented puzzle in that you have to have the unfortunate situation of having all of the pieces fall together for it to manifest itself.

An article published Friday Dec. 23 in the December 2011 issue of The Quarterly Review of Biology argues that multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system. Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism, in many ways more similar to coronary atherosclerosis (hardening of the arteries) than to other autoimmune diseases.

Framing MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide, Corthals says. She believes this new framework could help guide researchers toward new treatments and ultimately a cure for the disease.

It is also important to recognize that the aggregate contribution of germline genetic variants to the disease course of a given patient with MS may be modest. This is highlighted by observations that the clinical expression of MS may be very different even between monozygotic twin siblings who both have the disease. It is therefore likely that several postgermline events influence the clinical expression of MS.

A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10.

Hayes CE, et al. Show all
Med Hypotheses. 2008;71(1 ):85-90. Epub 2008 Apr 2.

Department of Biochemistry, University of
Wisconsin, Madison, 433 Babcock Drive, Madison,
WI 53706, USA. hayes@biochem. wisc.edu

Abstract
Multiple sclerosis (MS) is a neurodegenerative disease of uncertain etiology. In MS, neurodegeneration is thought to be secondary to
autoimmune-mediated damage. However, no cohesive explanation yet exists as to how environmental factors interact to induce a
neurodegenerative autoimmune response. Insufficient sunlight exposure and chronic viral infections have been proposed as unrelated
environmental risk factors for MS. We suggest that these risk factors may act synergistically to enable the pathogenic autoimmune response.
Low ultraviolet light (UVL) exposure depletes vitamin D3 stores, and low vitamin D3 levels correlate strongly with high MS risk. The central
nervous system converts vitamin D3 into 1,25 -dihydroxyvitamin D3 (1,25 -(OH)2 D3), a biologically active hormone with
anti-inflammatory and neuro-protective functions that depend on IL-10-producing regulatory lymphocytes. Herpesvirus infection also
correlates with MS risk. Some herpesviruses like Epstein-Barr virus produce an IL-10-like cytokine termed vIL-10.

We hypothesize that vIL-10 may induce a dysfunction of IL-10-producing regulatory lymphocytes, thereby undermining the protective
functions of sunlight, vitamin D3, and 1,25 -(OH)2D3. The vIL-10 could elicit a host immune response capable of neutralizing or depleting
IL-10, or the vIL-10 could compete with IL-10 but fail to perform an essential IL-10 function. In either case, the lack of sunlight exposure and
the herpes virus infection might synergize to induce a defect in IL-10-producing regulatory lymphocyte function that undermines self-tolerance
mechanisms and enables a pathogenic autoimmune response to neural proteins.