. Author manuscript; available in PMC: 2013 Sep 23.

Published in final edited form as: Clin Immunol. 2011 Dec 24;143(1):8–21. doi: 10.1016/j.clim.2011.10.007

Table 2.

Transmethylation effects in immune cell types.

Type of immunocytes	Studied aspect	Consequences	References
Immunocyte differentiation	-Selective demethylation or de novo methylation of genes in tissues or lineage-specific manner -Demethylation of Lck gene in T cells -Demethylation of Pou2af1 in B cells -Methylation of dachshund homologue 1 (Dach1) in common lymphoid progenitors and DN thymocytes -Histone modification as pre-priming marks of lineage differentiation	-Myeloid/lymphoid commitment -T cell/B cell commitment	[79]
Thymocyte development	-Demethylation of CD8α and CD8β genes	-Transition of double negative to double positive stage	[80,81]
	-Retention of demethylated CD8 genes	-Single-positive CD4⁺ T cells
	-SAHase inhibition	-Arrested development (CD8^lo and CD4⁺CD8⁺ double positive stages) -Not due to increased apoptosis -T cell-specific inhibition of co-receptor CD4 and CD8 mRNA	[31]
B cell/T cell	-Demethylation of TCRβ and Igκ loci -IgH locus: preference for D element pre-marked with histone modification -Plant homeodomain (PHD) of Rag2	-Increased gene accessibility allowing V(D)J rearrangement	[79–82]
CD4+ T cells
Th1	-Demethylation of the IFN-γ gene -Methylation of the IL-4 gene	-Control of IFN-γ gene accessibility by transcription factor T-bet	[80,84–87]
Th2	-Methylation of the IFN-γ gene -Demethylation of the IL-4 gene	-Control of IL-4 gene accessibility by transcription factor GATA-4
Th17	-Acetylation of histone H3 in the IL-17/IL-17F promoter region -Trimethylation of H3K4 in IL-17/IL-17F promoter region	-Transcription of IL-17 and IL-17F cytokines	[88,89]
nTreg	-Increased acetylation of histone H3 in FOXP3 promoter region -Trimethylation of H3K4 in FOXP3 promoter region -Complete DNA demethylation in the FOXP3 promoter	-nTreg phenotype -Requires complete DNA demethylation of FOXP3 for a permanent regulatory state	[90]
Human monocytes	-Adenosine deaminase inhibitor	-Increased intracellular SAH levels -Decreased chemotactic responsiveness and attendant morphologic changes	[21,22]
	-SAHase inhibition	-Decreased arachidonic acid release from membrane phospholipids -Decreased second messenger activation via phosphoinositide metabolism
Macrophages	-SAHase inhibition	-Normal antigen processing and presentation -Significant reduction of TNF-α	[33]
B cells	-SAHase inhibition	-No inhibition of B cell proliferation	[29]
T cells Mouse	-S-adenosyl-L-methionine burst	-High sensitivity of transmethylation inhibition	[24]
	-Irreversible SAHase inhibition	-Inhibition of conA stimulated-T cell proliferation and IL-2 production -Reduced OVA-specific T cell responses -Reduced anti-OVA antibody levels	[29,30]
	-Reversible SAHase inhibition	-No inhibition of conA stimulated-T cell proliferation or IL-2 production -Did inhibit IL-12p40 and TNF-α from monocytes	[37]