Human interleukin-15 improves engraftment of human T cells in NOD-SCID mice.
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 microg/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.
Sun
Anyuan
A
School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, China, and Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Wei
Haiming
H
Sun
Rui
R
Xiao
Weihua
W
Yang
Yongguang
Y
Tian
Zhigang
Z
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D006082:Graft Enhancement, Immunologic; D006801:Humans; D019409:Interleukin-15 / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous
D016207:Cytokines; D019409:Interleukin-15; D011994:Recombinant Proteins