Science & tech · 1997

Do all human respond to activation by undergoing cell death?

No. Th1 clones underwent Fas-mediated activation-induced cell death, while Th2 clones resisted it; a panel of Th0 clones included both sensitive and resistant clones.

Details

Researchers analyzed human T cell clones for susceptibility to activation-induced cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed only in Th1 clones and was mediated by Fas, whereas Th2 clones resisted AICD.

The researchers also analyzed a panel of Th0 clones, which can secrete both Th1 and Th2 cytokines. This group included both AICD-sensitive clones, called type A, and AICD-resistant clones, called type B. Resistance in Th2 and Th0-type B clones was not due to a lack of expression of the Fas receptor or its ligand.

Paradoxically, the AICD-resistant clones were susceptible to apoptosis when the Fas receptor was directly ligated by anti-Fas antibodies. However, prior activation of these resistant clones with monoclonal antibodies to the CD3/TCR complex induced resistance to Fas-mediated apoptosis.

The researchers concluded that the Fas-FasL pathway is critical for inducing AICD in T cells and that signals generated by CD3/TCR complex ligation can negatively regulate this pathway in AICD-resistant clones.

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