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Liou, H.C. et al.

c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function.

The TCR signals are essential for T cell activation and proliferation, primarily through the induction of cytokine and cytokine receptors. Several transcription factor families, including NF-kappaB/Rel, have been implicated in the regulation of cytokine gene expression in T cells in response to antigen, cytokine and mitogenic stimulation. In this study, we show that the mice with a null mutation in the lymphoid-specific c-Rel gene have normal development of lymphoid tissues and T cell compartment. However, T cells derived from the c-Rel knockout mice have several functional abnormalities. The c-Rel-deficient T lymphocytes fail to respond to activation and proliferation signals mediated by the TCR and mitogens in vitro. This is attributed to an impaired production of cytokines IL-2, IL-3 and granulocyte macrophage colony stimulating factor. In addition, the induction of IL-2R alpha chain is impaired in the c-Rel(-/-) T cells. The poor expression of cytokines and IL-2R alpha chain correlates with a reduced nuclear translocation of NF-kappaB components in c-Rel(-/-) T cells. Since activation is prerequisite for differentiation into effector cells, c-Rel(-/-) T cells failed to differentiate into cytotoxic T cells or Th cells without rescuing cytokines. However, upon supplement with exogenous IL-2, the c-Rel(-/-) cytotoxic T lymphocytes are able to execute cytotoxicity and the c-Rel(-/-) Th cells are capable of providing help to normal B cells. These data suggest that c-Rel is important for inducible cytokine and cytokine receptor expression, and a key regulator of early activation and proliferation in T cells.[1]

References

c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function. Liou, H.C., Jin, Z., Tumang, J., Andjelic, S., Smith, K.A., Liou, M.L. Int. Immunol. (1999) [Pubmed]

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