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Lack of activation induced cell death in human T blasts despite CD95L
up‐regulation: protection from apoptosis by MEK signalling
Author(s) -
Walker L. S. K.,
Mcleod J. D.,
Boulougouris G.,
Patel Y. I.,
Ellwood C. N.,
Hall N. D.,
Sansom D. M.
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00925.x
Subject(s) - microbiology and biotechnology , apoptosis , fas receptor , programmed cell death , t cell receptor , kinase , signal transduction , mapk/erk pathway , biology , mitogen activated protein kinase , jurkat cells , t cell , protein kinase a , cancer research , immunology , immune system , biochemistry
Summary 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.