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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

Anyuan Sun,1 Haiming Wei,1 Rui Sun,1,2 Weihua Xiao,1 Yongguang Yang,3 and Zhigang Tian1,2*

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.

* Corresponding author. Mailing address: School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, China. Phone: 86-551-360-7379. Fax: 86-551-360-6783. E-mail: tzg{at}ustc.edu.cn.

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.





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