IMPROVED ENGRAFTMENT OF HUMAN SPLEEN-CELLS IN NOD LTSZ-SCID SCID MICEAS COMPARED WITH C.B-17-SCID SCID MICE

T and B lymphocyte-deficient mice homozygous for the severe combined i mmunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral blood monon uclear cell engraftment are commonly observed, impeding full use of th is model. We now demonstrate that strain background in mice homozygous for the scid mutation is a strong determinant of levels of human lymp hocyte engraftment. NOD/LtSz-scid/scid mice support higher levels of e ngraftment of both human spleen and peripheral blood mononuclear cells than do C.B-17-scid/scid mice. We observed, using human spleen cell i njected scid mice, 1), high levels of engraftment of the host peripher al lymphoid tissues with human CD45(+) (leukocytes), CD3(+) (T cells), CD4(+) (helper/inducer), and CD8(+) (suppressor/cytotoxic) lymphoid c ells for up to 24 weeks in NOD/LtSz-scid/scid, but not in C.B-17-scid/ scid mice; 3), higher levels of serum immunoglobulin of human origin i n NOD/LtSz-scid/scid mice than in C.B-17-scid/scid mice; 4), histologi cal lesions characteristic of human anti-mouse xenoreactivity in NOD/L tSz-scid/scid mice; and 5), human origin antibodies against filarial a ntigens after engraftment with naive human spleen cells. The use of NO D/LtSz-scid/scid mice as recipients to achieve significantly enhanced human lymphopoietic cell engraftment will now enable human immunity to be more easily studied in animal models.