@article {24116,
	title = {Enhanced T cell function in a mouse model of human glycosylation},
	journal = {Journal of Immunology},
	volume = {191},
	number = {1},
	year = {2013},
	note = {<p>J Immunol. 2013 Jul 1;191(1):228-37. doi: 10.4049/jimmunol.1202905. Epub 2013 May 24.</p>
},
	month = {Jul 1},
	pages = {228-37},
	type = {Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t},
	edition = {2013/05/28},
	abstract = {<p>Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B- and C-related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah(-/-) mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah(-/-) T cells. Importantly, Cmah(-/-) mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah(-/-) mice make more lymphocytic choriomeningitis virus-specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases.</p>
},
	keywords = {Animals, CD4-Positive T-Lymphocytes/immunology/metabolism/virology, Cell Proliferation, Cells, Cultured, Dependovirus/genetics/immunology/metabolism, Glycosylation, Humans, Lymphocyte Activation/*genetics/*immunology, Lymphocytic choriomeningitis virus/ge},
	isbn = {1550-6606 (Electronic)00},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691298/},
	author = {Buchlis, G and Odorizzi, P and Soto, PC and Pearce, OM and Hui, DJ and Jordan, MS and Ajit Varki and Wherry, EJ and High, KA}
}
