Abstract:
:The generation of effective immunity requires that antigen-specific T cells are activated, clonally expanded and ultimately eliminated by apoptosis. The involvement of CD95-mediated apoptosis in T-cell elimination is well established, but the conditions which regulate the death pathway under normal circumstances are still emerging. Using superantigen-activated human T cells, we found that whilst T-cell receptor (TCR) signalling triggered up-regulation of CD95 ligand (CD95L), the majority of T cells were resistant to apoptosis induction, despite co-expressing high levels of CD95. Resistance was maintained following direct antibody-mediated cross-linking of CD95 and was not confined to early time periods following activation. Our data implicate TCR-derived signals in protection from apoptosis and reveal a role for the mitogen-activated protein (MAP) kinase pathway by use of a MAP kinase kinase (MEK) inhibitor. Collectively these data demonstrate that resistance to activation-induced cell death in human T cells is prolonged rather than transient, is not attributable to a lack of CD95L up-regulation and is due, at least in part, to signalling via the MEK pathway.
journal_name
Immunologyjournal_title
Immunologyauthors
Walker LS,McLeod JD,Boulougouris G,Patel YI,Ellwood CN,Hall ND,Sansom DMdoi
10.1046/j.1365-2567.1999.00925.xkeywords:
subject
Has Abstractpub_date
1999-12-01 00:00:00pages
569-75issue
4eissn
0019-2805issn
1365-2567pii
925journal_volume
98pub_type
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