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J. Exp. Med.,
Volume 189, Number 7, April 5, 1999 1073-1081
and NK1.1+ T Cells Reciprocally
Regulate Acute Graft versus Host Disease
By

From the * Department of Medicine, Division of Immunology and Rheumatology; the 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
Department of
Pediatrics; and the § Department of Pathology, Stanford University School of Medicine, Stanford,
California 94305
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
(IFN-
) and interleukin 4 (IL-4), and
the NK1.1
T cells secreted high levels of IFN-
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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