| First Author | Leveson-Gower DB | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 11 | Pages | 3220-9 |
| PubMed ID | 21258007 | Mgi Jnum | J:170509 |
| Mgi Id | MGI:4946589 | Doi | 10.1182/blood-2010-08-303008 |
| Citation | Leveson-Gower DB, et al. (2011) Low doses of natural killer T cells provide protection from acute graft-versus-host disease via an IL-4-dependent mechanism. Blood 117(11):3220-9 |
| abstractText | 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 x 10(4) cells suppress GVHD caused by 5.0 x 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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) 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. |
