Cross-linking of cell surface ganglioside GM1 induces the selective apoptosis of mature CD8(+) T lymphocytes

Nashar, Toufic O. and Williams, Neil A. and Hirst, Timothy R. (1996) Cross-linking of cell surface ganglioside GM1 induces the selective apoptosis of mature CD8(+) T lymphocytes. International Immunology, 8 (5). pp. 731-736. ISSN 0953-8178. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1093/intimm/8.5.731

Abstract

Gangliosides are glycosphingolipids found ubiquitously on the surface of mammalian cells, They contain a ceramide tail that is inserted into the membrane and exposed carbohydrate and sialic acid moieties, The non-toxic B subunit oligomer (EtxB) of Escherichia coil heat-labile enterotoxin (Etx) is a potent immunogen in vivo and has profound modulatory effects on EtxB-primed lymphocytes in vitro, properties which are dependent on its ability to bind to GM1 ganglioside receptors, Here, it is shown that cross-linking GM1 by EtxB causes a differential effect on mature CD4(+) and CD8(+) T cells from lymph node cultures proliferating in response to an unrelated antigen, ovalbumin, Addition of EtxB to such cultures led to the complete depletion of CD8(+) T cells compared with enhanced activation of CD4(+) T cells [as measured by expression of CD25 (IL-2R alpha)]. By contrast, addition of a mutant EtxB, EtxB(G33D), which does not bind to GM1, failed to trigger CD8(+) T cell depletion, When EtxB was added to isolated non-immune CD8(+) lymphocytes rapid (12-18 h) alterations in nuclear morphology and the appearance of sub-G(0)/G(1) levels of DNA were induced; properties which are characteristic of cells undergoing apoptosis, EtxB(G33D) failed to trigger apoptosis, indicating that the induction of the apoptotic signal was dependent on the binding of GM1, These findings provide an insight into the potent immunogenicity and immunomodulatory properties of E. coil enterotoxins as well as heralding a novel method for the selective induction of apoptosis in mature CD8(+) T lymphocytes.

Item Type: Article
Uncontrolled keywords: apoptosis; CD8; choleratoxin; E-coil enterotoxin; GM1; T lymphocyte
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: F.D. Zabet
Date Deposited: 11 Jun 2009 14:50
Last Modified: 19 Jun 2014 15:16
Resource URI: http://kar.kent.ac.uk/id/eprint/18704 (The current URI for this page, for reference purposes)
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