Murine IL-2 receptor beta chain blockade improves human leukocyte engraftment in SCID mice.
Severe combined immunodeficient (SCID) mice accept human xenografts and can act as a model for human immune functions. Murine natural killer cells (NK), however, represent an important barrier for the reconstitution of SCID mice with human peripheral blood leukocytes (Hu-PBL). We investigated the effect on Hu-PBL survival of pretreatment with TM-beta1, a rat monoclonal antibody for the mouse IL-2 receptor beta chain. TM-beta1 greatly improved the survival of Hu-PBL. Human lymphocytes, predominantly T cells, survived in the peritoneum and infiltrated spleen and lungs already 1 week after engraftment and liver and thymus from 2 weeks on. Secondary humoral responses were evaluated with Hu-PBL from a donor immune to hepatitis-B surface Ag (HBsAg) and tetanus toxoid (TT). TM-beta1 pretreatment enhanced the recall Ig response to HBsAg and did not affect the baseline anti-TT Ig production. In conclusion, TM-beta1 pretreatment of SCID mice significantly improves the survival and functionality of the Hu-PBL graft.
Tournoy
K G
KG
University Hospital Gent, Department of Respiratory Diseases, Belgium. kurt.tournoy@rug.ac.be
Depraetere
S
S
Meuleman
P
P
Leroux-Roels
G
G
Pauwels
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002470:Cell Survival; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation*; D051379:Mice; D016513:Mice, SCID; D010529:Peritoneal Cavity; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2