Combinations of CD45 isoforms are crucial for immune function and disease

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ritu DawesE Z Tchilian

Abstract

Expression of the CD45 Ag in hemopoietic cells is essential for normal development and function of lymphocytes, and both mice and humans lacking expression exhibit SCID. Human genetic variants of CD45, the exon 4 C77G and exon 6 A138G alleles, which alter the pattern of CD45 isoform expression, are associated with autoimmune and infectious diseases. We constructed transgenic mice expressing either an altered level or combination of CD45 isoforms. We show that the total level of CD45 expressed is crucial for normal TCR signaling, lymphocyte proliferation, and cytokine production. Most importantly, transgenic lines with a normal level, but altered combinations of CD45 isoforms, CD45(RABC/+) and CD45(RO/+) mice, which mimic variant CD45 expression in C77G and A138G humans, show more rapid onset and increased severity of experimental autoimmune encephalomyelitis. CD45(RO/+) cells produce more TNF-alpha and IFN-gamma. Thus, for the first time, we have shown experimentally that it is the combination of CD45 isoforms that affects immune function and disease.

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Citations

Aug 7, 2008·Journal of Cutaneous Pathology·Cynthia M Magro, Molly E Dyrsen
May 2, 2008·International Immunology·Robert J SalmondDenis R Alexander
Apr 20, 2006·International Immunology·Zhe LiuElma Z Tchilian
Nov 19, 2009·The Journal of Biological Chemistry·Lesley A EarlLinda G Baum
May 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zuopeng WuChristopher C Goodnow
Sep 11, 2009·PLoS Neglected Tropical Diseases·Jacqueline Araújo FiuzaRodrigo Correa-Oliveira
Nov 15, 2006·Clinical and Experimental Immunology·E Z TchilianP C L Beverley
Sep 4, 2009·Rejuvenation Research·Johannes HoferMartina Prelog
Jul 24, 2007·Blood·Stephen M JacksonJ Donald Capra
May 1, 2021·Genes·Zhongjing Su, Dongyang Huang

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