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Induction of signalling anergy via the T‐cell receptor in cultured Jurkat T cells by pre‐exposure to a filarial nematode secreted product
Author(s) -
Harnett Margaret M.,
Deehan Maureen R.,
Williams Denise M.,
Harnett William
Publication year - 1998
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1046/j.1365-3024.1998.00181.x
Subject(s) - biology , jurkat cells , fyn , t cell receptor , microbiology and biotechnology , immunology , signal transduction , phosphorylcholine , kinase , t cell , tyrosine kinase , immune system , biochemistry
Filarial nematodes constitute major causes of morbidity in the Tropics. The worms have a life‐span exceeding five years, a longevity which is considered to reflect at least in part, their ability to interfere with host lymphocyte responsiveness. To date the molecular mechanisms underlying this ability have not been defined but we now demonstrate that ES‐62, a phosphorylcholine (PC)‐containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to render Jurkat T cells anergic to intracellular signalling via the antigen receptor (TCR). In particular, ES‐62 acts by modulating activation of the tyrosine kinases Fyn, Lck and ZAP‐70 leading to selective disruption of TCR coupling to the phospholipase D, protein kinase C, phosphoinositide‐3‐kinase and RasMAPkinase signalling cascades. These cascades are key elements in the transduction of transcriptional and proliferative signals following ligation of TCR. As PC‐containing secreted products (PC‐ES) are also released by human filarial parasites, our data suggest that PC‐ES may play a role in the induction of T lymphocyte hyporesponsiveness observed during filarial infections.