The Journal of Experimental Medicine
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*Bone Marrow Transplantation
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© The Rockefeller University Press, 0022-1007/1999/4/1073/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 7, April 5, 1999 1073-1081


Articles

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

Defu Zeng*, David Lewis{ddagger}, Sussan Dejbakhsh-Jones*, Fengshuo Lan*, Marcos García-Ojeda*, Richard Sibley§, and Samuel Strober*

From the * Department of Medicine, Division of Immunology and Rheumatology; the {ddagger} Department of Pediatrics; and the § Department of Pathology, Stanford University School of Medicine, Stanford, California 94305

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 {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–/– 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.

Key Words: bone marrow transplantation • immune regulation • regulatory T cells • cytokines • interleukin 4


Address correspondence to Samuel Strober, Division of Immunology and Rheumatology, Stanford University School of Medicine, 300 Pasteur Dr., Rm. S105B, Stanford, CA 94305. Phone: 650-723-6500; Fax: 650-725-6104; E-mail: sstrober{at}stanford.edu

Abbreviations used: TCD, T cell–depleted.


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