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Donor bone marrow type II (non-Valpha14Jalpha18 CD1d-restricted) NKT cells suppress graft-versus-host disease by producing IFN-gamma and IL-4

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Authors
Kim, Ji Hyung; Choi, Eun Young; Chung, Doo Hyun
Issue Date
2007
Publisher
American Association of Immunologists
Citation
J. Immunol. 179: 6579-6587
Keywords
Antigens, CD1/genetics/*immunology/metabolismAntigens, CD1dApoptosis/genetics/immunologyBone Marrow TransplantationGraft vs Host Disease/*immunology/metabolism/pathologyInterferon-gamma/biosynthesis/genetics/*immunologyInterleukin-4/biosynthesis/genetics/*immunologyKiller Cells, Natural/*immunology/metabolism/pathologyMice, Inbred BALB CMice, KnockoutReceptors, Antigen, T-Cell, alpha-beta/genetics/*immunology/metabolismTh2 Cells/*immunology/metabolism/pathology
Abstract
NKT cells in donor bone marrow (BM) have been demonstrated to protect against graft-vs-host disease (GVHD) following BM transplantation. Murine NKT cells are divided into two distinct subsets based on the invariant Valpha14Jalpha18 TCR expression. However, details of the subset and mechanisms of the BM NKT cells involved in suppressing GVHD have not been clarified. Irradiated BALB/c or C3H/HeN mice administered B6 or Jalpha18(-/-) BM cells show attenuation of GVHD, whereas recipients given CD1d(-/-) BM cells did not show attenuation. Moreover, coinjection of BM non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cells and CD1d(-/-) BM cells suppressed GVHD, whereas coinjection of BM Valpha14Jalpha18 TCR (type I) NKT cells did not. These protective effects on GVHD depended upon IFN-gamma-producing type II NKT cells, which induced the apoptosis of donor T cells. The splenocytes of mice administered BM cells from B6.IL-4(-/-) or Jalpha18(-/-)IL-4(-/-) mice produced lower levels of IL-4 and IL-10 than the splenocytes of mice transplanted with BM cells from B6, B6.IFN-gamma(-/-), Jalpha18(-/-), or Jalpha18(-/-)IFN-gamma(-/-) mice. Taken together, our results show that IFN-gamma-producing BM type II NKT cells suppress GVHD by inducing the apoptosis of donor T cells, while IL-4-producing BM type II NKT cells protect against GVHD by deviating the immune system toward a Th2-type response.
ISSN
0022-1767 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17982047

http://hdl.handle.net/10371/10036
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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