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Clinical and Vaccine Immunology, February 2006, p. 227-234, Vol. 13, No. 2
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.2.227-234.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Interleukin-15 Improves Engraftment of Human T Cells in NOD-SCID Mice

School of Life Sciences, University of Science and Technology of China, Hefei 230027,¹ School of Pharmaceutical Sciences, Shandong University, Jinan 250021, China,² Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129³

Received 8 August 2005/ Returned for modification 15 September 2005/ Accepted 23 November 2005

Human nonobese diabetic-severe combined immune deficiency (NOD-SCID) mouse chimeras have been widely used as an in vivo model to assess human immune function. However, only a small fraction of transferred human T lymphocytes can be detected in human peripheral blood lymphocyte (huPBL)-NOD-SCID chimeras. To improve the reconstitution of human T lymphocytes in NOD-SCID mice, the use of recombinant human interleukin-15 (rhIL-15) as a stimulator of human lymphocytes was explored. Administration of rhIL-15 after transplantation of huPBLs into NOD-SCID mice increased reconstitution of human T lymphocytes in a dose-dependent manner, with an optimal dosage of 1 µg/mouse. The number of human T lymphocytes (HLA-ABC⁺ CD3⁺) in the lymphoid organs or tissue of rhIL-15-treated huPBL-NOD-SCID mice increased 11- to 80-fold, and phytohemagglutinin-induced T-lymphocyte proliferation and cytokine production were significantly enhanced. Additionally, although mature human cells have not been thought to enter the murine thymus, human T lymphocytes were detected in the huPBL-NOD-SCID thymus after rhIL-15 treatment. Thus, rhIL-15 can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful in clinical treatment of T-cell deficiencies.