New T cell synthesis is needed in order for T cell clones to expand and respond properly to an immune assault. T cells are needed to help to control the B cells and to balance TH1 and TH2 responses. If there are methylation cycle problems or mutations, you may have trouble making the bases that are needed for new DNA synthesis. If you cannot make new DNA, then you cannot make new T cells and as a result you may lack immune system regulatory cells. The immune system has the B cell "arm" that makes antibodies, known as humoral immunity and the T cell "arm" known as cellular immunity. If you are having trouble making new T cells, in particular, T suppressor cells, then the immune response may become more heavily weighted in the direction of B cells. B cell skewed individual has the ability to respond by making antibodies (or autoantibodies) in high numbers to attempt to overcome the T cell deficiency that fights infection. B cell clones expand to be available for the future. This scenario creates a somewhat greater need for new DNA synthesis.

Methylation also plays a role in the ability of the immune system to recognize foreign bodies or antigens that it needs to respond to. Research has shown that methylation is decreased in humans with autoimmune conditions. Impaired methylation of T cells may be involved in the production of autoantibodies. Studies from patients with systemic lupus erythrematosis (SLE) have shown that their T cells are undermethylated. As proper methylation function is restored, immune system regulation should slowly recover.