CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

Figure 3

Proposed genetic deficiency of CD8+ T cells underlying the development of chronic autoimmune diseases. The upper green panel on the graph represents health, the middle orange panel, the development of mild autoimmune disease (mild autoimmunity) and the lower red panel the development of severe progressive autoimmune disease (Severe autoimmunity). In normal individuals (Health) the number of CD8+ T cells declines with increasing age but still remains sufficient to control EBV infection. In individuals with a mild genetic deficiency of CD8+ T cells, the deficiency is aggravated by increasing age eventually leading to insufficient CD8+ T cells to control EBV infection. In individuals carrying HLA class II or class I genes predisposing to specific autoimmune diseases, this leads to the accumulation of EBV-infected B cells in the target organ and the development of autoimmune disease, which progresses in severity as the CD8+ T-cell count further declines with age and as the EBV load in the target organ subsequently increases. In individuals with a severe genetic deficiency of CD8+ T cells, autoimmune diseases develop at a younger age and progress more rapidly. Deprivation of sunlight and vitamin D at higher latitudes aggravates the genetic CD8+ T-cell deficiency and increases the incidence and progression of autoimmune disease.