@article {13009,
	title = {Loss of Siglec expression on T lymphocytes during human evolution},
	journal = {Proc Natl Acad Sci U S A},
	volume = {103},
	number = {20},
	year = {2006},
	note = {<p>Proc Natl Acad Sci U S A. 2006 May 16;103(20):7765-70. Epub 2006 May 8</p>
},
	month = {May 16},
	pages = {7765-70},
	type = {Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}t},
	edition = {2006/05/10},
	abstract = {<p>We report here that human T cells give much stronger proliferative responses to specific activation via the T cell receptor (TCR) than those from chimpanzees, our closest evolutionary relatives. Nonspecific activation using phytohemagglutinin was robust in chimpanzee T cells, indicating that the much lower response to TCR simulation is not due to any intrinsic inability to respond to an activating stimulus. CD33-related Siglecs are inhibitory signaling molecules expressed on most immune cells and are thought to down-regulate cellular activation pathways via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Among human immune cells, T lymphocytes are a striking exception, expressing little to none of these molecules. In stark contrast, we find that T lymphocytes from chimpanzees as well as the other closely related "great apes" (bonobos, gorillas, and orangutans) express several CD33-related Siglecs on their surfaces. Thus, human-specific loss of T cell Siglec expression occurred after our last common ancestor with great apes, potentially resulting in an evolutionary difference with regard to inhibitory signaling. We confirmed this by studying Siglec-5, which is prominently expressed on chimpanzee lymphocytes, including CD4 T cells. Ab-mediated clearance of Siglec-5 from chimpanzee T cells enhanced TCR-mediated activation. Conversely, primary human T cells and Jurkat cells transfected with Siglec-5 become less responsive; i.e., they behave more like chimpanzee T cells. This human-specific loss of T cell Siglec expression associated with T cell hyperactivity may help explain the strikingly disparate prevalence and severity of T cell-mediated diseases such as AIDS and chronic active hepatitis between humans and chimpanzees.</p>
},
	keywords = {*Biological Evolution, Animals, Antigens, B-Lymphocytes/cytology/immunology, Calcium/metabolism, CD/*immunology, Cell Proliferation, Differentiation, Down-Regulation, Humans, Lectins/*immunology, Lymphocyte Activation, Myelomonocytic/*immunology},
	isbn = {0027-8424 (Print)0027-84},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/16682635},
	author = {Nguyen, D. H. and Hurtado-Ziola, N. and Gagneux, P. and Ajit Varki}
}
