Bone Marrow NK1.1 and NK1.1+ T Cells Reciprocally Regulate Acute Graft versus Host Disease

D Zeng, D Lewis, S Dejbakhsh-Jones, F Lan… - The Journal of …, 1999 - rupress.org
D Zeng, D Lewis, S Dejbakhsh-Jones, F Lan, M García-Ojeda, R Sibley, S Strober
The Journal of experimental medicine, 1999rupress.org
Sorted CD4+ and CD8+ T cells from the peripheral blood or bone marrow of donor C57BL/6
(H-2b) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by
injecting the cells, along with stringently T cell–depleted donor marrow cells, into lethally
irradiated BALB/c (H-2d) host mice. The peripheral blood T cells were at least 30 times more
potent than the marrow T cells in inducing lethal GVHD. As NK1. 1+ T cells represented< 1%
of all T cells in the blood and∼ 30% of T cells in the marrow, the capacity of sorted marrow …
Sorted CD4+ and CD8+ T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2b) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell–depleted donor marrow cells, into lethally irradiated BALB/c (H-2d) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1+ T cells represented <1% of all T cells in the blood and ∼30% of T cells in the marrow, the capacity of sorted marrow NK1.1 CD4+ and CD8+ T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1+ T cells suppressed GVHD. The marrow NK1.1+ T cells secreted high levels of both interferon γ (IFN-γ) and interleukin 4 (IL-4), and the NK1.1 T cells secreted high levels of IFN-γ with little IL-4. Marrow NK1.1+ T cells obtained from IL-4−/− rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1 and NK1.1+ T cell subsets via their differential production of cytokines.
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