The NF kappa B heterodimer/homodimer balance and IL-1-stimulated IL-2 production in murine T lymphocytes.

Activation of NF kappa B is considered one way IL-1 exerts its costimulatory effect on T cell activation and IL-2 production. However, T helper 2 cells do not synthesize IL-2 upon IL-1 stimulation, although they depend on IL-1 for proliferation. The involvement of NF kappa B in IL-2 production was therefore addressed in two different murine cell lines: D10N, a T helper 2 cell line that does not synthesize IL-2, and EL4 6.1., a thymoma cell line producing IL-2 when stimulated with IL-1. In both cell types IL-1 activated the DNA binding activity of the NF kappa B heterodimers p50/65 and p50/c-rel via the IL-1 type I receptor. In D10N cells, however, the p50/p50 homodimer is present in large amounts in unstimulated cells, whereas the heterodimers were only activated by IL-1-treatment. In contrast, only marginal amounts of the p50/p50 homodimer were found in EL4 6.1. cells, but a strong activation of heterodimers was induced by IL-1. The findings are compatible with the concept of p50 homodimer being inhibitory by replacing the p50/p65 or p50/c-rel heterodimer from nuclear kappa B binding sites. The inability of D10N cells to respond to IL-1 exposure with IL-2 formation might therefore be due to their high constitutive levels of p50 homodimers.