{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:59:50Z","timestamp":1790654390891,"version":"4.1.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although humans and chimpanzees share &amp;gt;99% identity in alignable protein sequences, they differ surprisingly in the incidence and severity of some common diseases. In general, humans infected with various viruses, such as HIV and hepatitis C virus, appear to develop stronger reactions and long-term complications. Humans also appear to suffer more from other diseases associated with over-reactivity of the adaptive immune system, such as asthma, psoriasis, and rheumatoid arthritis. In this study, we show that human T cells are more reactive than chimpanzee T cells to a wide variety of stimuli, including anti-TCR Abs of multiple isotypes, l-phytohemagglutin, Staphylococcus aureus superantigen, a superagonist anti-CD28 Ab, and in MLRs. We also extend this observation to B cells, again showing a human propensity to react more strongly to stimuli. Finally, we show a relative increase in activation markers and cytokine production in human lymphocytes in response to uridine-rich (viral-like) ssRNA. Thus, humans manifest a generalized lymphocyte over-reactivity relative to chimpanzees, a finding that is correlated with decreased levels of inhibitory sialic acid-recognizing Ig-superfamily lectins (Siglecs; particularly Siglec-5) on human T and B cells. Furthermore, Siglec-5 levels are upregulated by activation in chimpanzee but not human lymphocytes, and human T cell reactivity can be downmodulated by forced expression of Siglec-5. Thus, a key difference in the immune reactivity of chimp and human lymphocytes appears to be related to the differential expression of Siglec-5. Taken together, these data may help explain human propensities for diseases associated with excessive activation of the adaptive immune system.<\/jats:p>","DOI":"10.4049\/jimmunol.0903420","type":"journal-article","created":{"date-parts":[[2010,3,16]],"date-time":"2010-03-16T04:11:09Z","timestamp":1268712669000},"page":"4185-4195","source":"Crossref","is-referenced-by-count":48,"title":["Relative Over-Reactivity of Human versus Chimpanzee Lymphocytes: Implications for the Human Diseases Associated with Immune Activation"],"prefix":"10.1093","volume":"184","author":[{"given":"Paula C.","family":"Soto","sequence":"first","affiliation":[{"name":"*Department of Medicine,"},{"name":"\u2020Department of Cellular and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance L.","family":"Stein","sequence":"additional","affiliation":[{"name":"*Department of Medicine,"},{"name":"\u2020Department of Cellular and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hurtado-Ziola","sequence":"additional","affiliation":[{"name":"*Department of Medicine,"},{"name":"\u2020Department of Cellular and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Hedrick","sequence":"additional","affiliation":[{"name":"\u2021Division of Biological Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"\u00a7Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,4,15]]},"reference":[{"key":"2023010203132536900_r1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nature04072","article-title":"Initial sequence of the chimpanzee genome and comparison with the human genome.","volume":"437","author":"Chimpanzee Sequencing and Analysis Consortium","year":"2005","journal-title":"Nature"},{"key":"2023010203132536900_r2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1101\/gr.10.8.1065","article-title":"A chimpanzee genome project is a biomedical imperative.","volume":"10","author":"Varki","year":"2000","journal-title":"Genome Res."},{"key":"2023010203132536900_r3","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1101\/gr.3737405","article-title":"Comparing the human and chimpanzee genomes: searching for needles in a haystack.","volume":"15","author":"Varki","year":"2005","journal-title":"Genome Res."},{"key":"2023010203132536900_r4","article-title":"The evolution of the human lifespan and diseases of aging: roles of infection, inflammation, and nutrition.","author":"Finch","year":"2009","journal-title":"Proc. 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