Cancer Institute A national cancer institute
designated cancer center

Robert Negrin

Publication Details

  • Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4-dependent mechanism BLOOD Leveson-Gower, D. B., Olson, J. A., Sega, E. I., Luong, R. H., Baker, J., Zeiser, R., Negrin, R. S. 2011; 117 (11): 3220-3229

    Abstract:

    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-? (IFN-?) and tumor necrosis factor-? (TNF-?) 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.

    View details for DOI 10.1182/blood-2010-08-303008

    View details for Web of Science ID 000288496300034

    View details for PubMedID 21258007

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