Relative over-reactivity of human versus chimpanzee lymphocytes: implications for the human diseases associated with immune activation

Bibliographic Collection: 
CARTA-Inspired Publication, APE
Publication Type: Journal Article
Authors: Soto, P. C.; Stein, L. L.; Hurtado-Ziola, N.; Hedrick, S. M.; Varki, A.
Year of Publication: 2010
Journal: J Immunol
Volume: 184
Edition: 2010/03/17
Number: 8
Pagination: 4185-95
Date Published: Apr 15
Type of Article: Comparative StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
Publication Language: eng
ISBN Number: 1550-6606 (Electronic)00
Keywords: *Adaptive Immunity/genetics, Acquired Immunodeficiency Syndrome/immunology/metabolism/pathology, Animals, Antigens, B-Lymphocytes/*immunology/, CD/biosynthesis/genetics/physiology, Differentiation, Myelomonocytic/biosynthesis/genetics/physiology
Abstract:

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.

Notes:

J Immunol. 2010 Apr 15;184(8):4185-95. doi: 10.4049/jimmunol.0903420. Epub 2010 Mar 15.

DOI: 10.4049/jimmunol.0903420
Custom 2:

3085894

Author Address:

Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

Export: