Journal
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
Volume 95, Issue 12, Pages 2111-2118Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2010.028829
Keywords
NF-kappa B; NF-kappa B inducing kinase; NIK; graft-versus-host disease
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Funding
- MF: FIS [P1040993, SAF2005-02220, SAF2007-61716]
- Spanish Ministry of Science [RD06/0021/0016]
- European Union [LSHM-CT-2004-005033]
- Comunidad de Madrid [S-SAL-0159/2006]
- Instituto de Salud Carlos III [MR: PI04/1347, PI07/0907]
- Fundacion Mutua Madrilena
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Background Donor T lymphocytes are directly responsible for graft-versus-host disease. Molecules important in T-cell function may, therefore, be appropriate targets for graft-versus-host disease therapy and/or prophylaxis. Here we analyzed whether nuclear factor-kappa B inducing kinase might have a role in graft-versus-host disease. Design and Methods We studied the expression of nuclear factor-kappa B inducing kinase in human samples from patients with graft-versus-host disease. We also explored the effect of nuclear factor-kappa B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-kappa B inducing kinase) and C57BL/6 mice (control). Results We detected expression of nuclear factor-kappa B inducing kinase in T-lymphocytes in the pathological lesions of patients with acute graft-versus-host disease. Mice transplanted with aly/aly T lymphocytes did not develop graft-versus-host disease at all, while mice receiving C57BL/6 cells died of a lethal form of the disease. Deficiency of nuclear factor-kappa B inducing kinase did not affect the engrafting ability of donor T cells, but severely impaired their expansion capacity early after transplantation, and aly/aly T cells showed a higher proportion of apoptosis than did C57BL/6 T cells. Effector T lymphocytes were the T-cell subset most affected by nuclear factor-kappa B inducing kinase deficiency. We also detected lower amounts of inflammatory cytokines in the serum of mice receiving aly/aly T cells than in the serum of mice receiving C57BL/6 T cells. Conclusions Our results show that nuclear factor-kappa B inducing kinase has a role in graft-versus-host disease by maintaining the viability of activated alloreactive T lymphocytes.
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