%0 Journal Article %J J Immunol %D 2010 %T Relative over-reactivity of human versus chimpanzee lymphocytes: implications for the human diseases associated with immune activation %A Soto, P. C. %A Stein, L. L. %A Hurtado-Ziola, N. %A Hedrick, S. M. %A Ajit Varki %K *Adaptive Immunity/genetics %K Acquired Immunodeficiency Syndrome/immunology/metabolism/pathology %K Animals %K Antigens %K B-Lymphocytes/*immunology/ %K CD/biosynthesis/genetics/physiology %K Differentiation %K Myelomonocytic/biosynthesis/genetics/physiology %X

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.

%B J Immunol %7 2010/03/17 %V 184 %P 4185-95 %8 Apr 15 %@ 1550-6606 (Electronic)00 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/20231688 %9 Comparative StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't %2 3085894 %R 10.4049/jimmunol.0903420