Regulation of human short-term repopulating cell (STRC) engraftment in NOD/SCID mice by host CD122+ cells.
OBJECTIVE
NOD/SCID and NOD/SCID B2m(null) mice are used for the in vivo study of human hematopoietic stem cells (HSC). A previously unrecognized HSC in cord blood, termed short-term repopulating cell (STRC), has been identified using NOD/SCID B2m(null) mice. However, only low levels of STRC engraft in NOD/SCID mice, presumably due to their higher levels of NK cell activity. The objective of these studies was to deplete NK cells both by genetic manipulation of the hosts and by antibody depletion of cell populations that may regulate engraftment with human STRC.


METHODS
C57BL/6-SCID mice and immunodeficient NOD mice genetically deleted in NK cell activity were injected intravenously with human cord blood cells to quantify STRC engraftment. Cohorts of these mice were also treated with anti-NK1.1 or anti-CD122 (IL-2r beta-chain) antibodies.


RESULTS
Human STRC fail to engraft in C57BL/6-SCID mice treated with anti-NK1.1 or with anti-CD122 antibody that targets mouse NK and myeloid cells. NOD/SCID mice, NOD-Rag1(null) mice, and NOD-Rag1(null)Pfp(null) mice that are genetically deleted in NK cell cytotoxic activity support only low levels of STRC engraftment. In contrast, STRC engraft at high levels in all three strains of immunodeficient NOD mice treated with anti-CD122 antibody.


CONCLUSIONS
Injection of anti-CD122 antibody leads to high levels of STRC engraftment in immunodeficient NOD mice, but not in C57BL/6-SCID mice. These data document that depletion of NK cells is required, and that additional murine host innate immune factors, presumably myeloid cells, are important in regulating human STRC engraftment.
Shultz
Leonard D
LD
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA. lds@jax.org
Banuelos
Scott J
SJ
Leif
Jean
J
Appel
Michael C
MC
Cunningham
Melody
M
Ballen
Karen
K
Burzenski
Lisa
L
Greiner
Dale L
DL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D008212:Lymphocyte Depletion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D022423:Myeloid Cells / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013997:Time Factors; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2