MURINE IL-2 RECEPTOR-BETA CHAIN BLOCKADE IMPROVES HUMAN-LEUKOCYTE ENGRAFTMENT IN SCID MICE

Severe combined immunodeficient (SCID) mice accept human xenografts an d can act as a model for human immune functions. Murine natural killer cells (NK), however, represent an important barrier for the reconstit ution of SCID mice with human peripheral blood leukocytes (Hu-PBL). We investigated the effect on Hu-PBL survival of pretreatment with TM-be ta 1, a rat monoclonal antibody for the mouse IL-2 receptor beta chain . TM-beta 1 greatly improved the survival of Hu-PBL. Human lymphocytes , predominantly T cells, survived in the peritoneum and infiltrated sp leen and lungs already 1 week after engraftment and liver and thymus f rom 2 weeks on. Secondary humoral responses were evaluated with Hu-PBL from a donor immune to hepatitis-B surface Ag (HBsAg) and tetanus tor oid (TT). TM-beta 1 pretreatment enhanced the recall Ig response to HB sAg and did not affect the baseline anti-TT Ig production. In conclusi on, TM-beta 1 pretreatment of SCID mice significantly improves the sur vival and functionality of the HU-PBL graft.