Redox Mechanisms in T Cell Activation

A variety of anti-oxidants, including free radical scavengers and iron chelators, inhibit the proliferation of mitogenstimulated T lymphocytes in vitro. These agents do not operate by inhibiting the induction of omithine decarboxylase activity. Phorbol myristate acetate induces formation of reactive oxygen species in T cell-enriched populations. Flow cytometry has identified this reactive oxygen within the T lymphocytes themselves, though other cells may contribute indirectly. The binding to DNA of the transcription factors AP-1 and NF-kB is increased during the commitment period, 2–4 hours after mitogen addition to T lymphocytes, and this binding is inhibited by the anti-oxidant aminothiol compound, cysteamine. Intracellular oxidant formation in mitogen-stimulated T cells might activate transcription factors, allowing their translocation into the nucleus and subsequent reduction and binding to DNA, thereby inducing early gene expression. Since the replication of the human immunodeficiency virus-1 is linked to NF-kB and can be inhibited by some anti-oxidants, it is possible that this virus is stimulated to replicate by the intracellular oxidative events that we have shown to be an obligatory step in T lymphocyte recruitment into the cell cycle.