Relative over-reactivity of human versus chimpanzee lymphocytes: implications for the human diseases associated with immune activation.
Although humans and chimpanzees share >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.
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Paula C
PC
Soto
Lance L
LL
Stein
Nancy
N
Hurtado-Ziola
Stephen M
SM
Hedrick
Ajit
A
Varki
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006526:Hepatitis C / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D037102:Lectins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology*; D002679:Pan troglodytes / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006131:Growth Inhibitors; D037102:Lectins; D011956:Receptors, Cell Surface; C514213:SIGLEC14 protein, human; C114531:SIGLEC5 protein, human