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Matsumoto, M. et al.

Matsumoto, Yamada, Yoshinaga, Boone, Horan, Fujita, Li, Mitani,

Essential role of NF-kappa B- inducing kinase in T cell activation through the TCR/CD3 pathway.

NF-kappa B-inducing kinase (NIK) is involved in lymphoid organogenesis in mice through lymphotoxin-beta receptor signaling. To clarify the roles of NIK in T cell activation through TCR/CD3 and costimulation pathways, we have studied the function of T cells from aly mice, a strain with mutant NIK. NIK mutant T cells showed impaired proliferation and IL-2 production in response to anti-CD3 stimulation, and these effects were caused by impaired NF-kappa B activity in both mature and immature T cells; the impaired NF-kappa B activity in mature T cells was also associated with the failure of maintenance of activated NF-kappa B. In contrast, responses to costimulatory signals were largely retained in aly mice, suggesting that NIK is not uniquely coupled to the costimulatory pathways. When NIK mutant T cells were stimulated in the presence of a protein kinase C (PKC) inhibitor, proliferative responses were abrogated more severely than in control mice, suggesting that both NIK and PKC control T cell activation in a cooperative manner. We also demonstrated that NIK and PKC are involved in distinct NF-kappa B activation pathways downstream of TCR/CD3. These results suggest critical roles for NIK in setting the threshold for T cell activation, and partly account for the immunodeficiency in aly mice.[1]

References

Essential role of NF-kappa B-inducing kinase in T cell activation through the TCR/CD3 pathway. Matsumoto, M., Yamada, T., Yoshinaga, S.K., Boone, T., Horan, T., Fujita, S., Li, Y., Mitani, T. J. Immunol. (2002) [Pubmed]

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