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.
Soto
Paula C
PC
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Stein
Lance L
LL
Hurtado-Ziola
Nancy
N
Hedrick
Stephen M
SM
Varki
Ajit
A
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