Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease

Sorted CD4(+) and CD8(+) T cells from the peripheral blood or bone marrow o f donor C57BL/6 (H-2(b)) mice were tested for their capacity to induce graf t-versus-host disease (GVHD) by injecting the cells, along with stringently T cell-depleted donor I-narrow cells, into lethally irradiated BALB/c (H-2 (d)) host mice. The peripheral blood T cells were at least 30 times more po tent than the marrow T cells in inducing lethal GVHD. As NK1.1(+) T cells r epresented <1% of all T cells in the blood and similar to 30% of T cells in the marrow, the capacity of sorted marrow NK1.1(-) CD4(+) and CD8(+) T cel ls to induce GVHD was tested. The latter cells had markedly increased poten cy, and adding back marrow NK1.1(+) T cells suppressed GVHD. The marrow NK1 .1(+) T cells secreted high levels of both interferon gamma (IFN-gamma) and interleukin 4 (IL-4), and the NK1.1(-) T cells secreted high levels of IFN -gamma with little IL-4. Marrow NK1.1(+) T cells obtained from IL-4(-/-) ra ther than wild-type C57BL/6 donors not only failed to prevent GVHD but actu ally increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1(-) and NK1.1(+) T cell subsets via t heir differential production of cytokines.