| Autor: |
Leveson-Gower DB; Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA, USA., Olson JA, Sega EI, Luong RH, Baker J, Zeiser R, Negrin RS |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2011 Mar 17; Vol. 117 (11), pp. 3220-9. Date of Electronic Publication: 2011 Jan 21. |
| DOI: |
10.1182/blood-2010-08-303008 |
| Abstrakt: |
CD4(+) natural killer T (NKT) cells, along with CD4(+)CD25(+) regulatory T cells (Tregs), are capable of controlling aberrant immune reactions. We explored the adoptive transfer of highly purified (> 95%) CD4(+)NKT cells in a murine model of allogeneic hematopoietic cell transplantation (HCT). NKT cells follow a migration and proliferation pattern similar to that of conventional T cells (Tcons), migrating initially to secondary lymphoid organs followed by infiltration of graft-versus-host disease (GVHD) target tissues. NKT cells persist for more than 100 days and do not cause significant morbidity or mortality. Doses of NKT cells as low as 1.0 × 10(4) cells suppress GVHD caused by 5.0 × 10(5) Tcons in an interleukin-4 (IL-4)-dependent mechanism. Protective doses of NKT cells minimally affect Tcon proliferation, but cause significant reductions in interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production by donor Tcons and in skin, spleen, and gastrointestinal pathology. In addition, NKT cells do not impact the graft-versus-tumor (GVT) effect of Tcons against B-cell lymphoma-1 (BCL-1) tumors. These studies elucidate the biologic function of donor-type CD4(+)NKT cells in suppressing GVHD in an allogeneic transplantation setting, demonstrating clinical potential in reducing GVHD in HCT. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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