Human peripheral blood leukocyte engraftment into SCID mice: Critical roleof CD4(+) T cells

We examined the influence of donor T lymphocytes on human peripheral blood leukocytes (PBL) engraftment into severe combined immune deficient (SLID) m ice. Mice were injected with unfractionated or subset-depleted human PBL, a nd treated at various times with OKT3, a cytotoxic monoclonal antibody agai nst human CD3+ T lymphocytes. PBL engraftment, high levels of human Ig, and high incidence of lymphoproliferative disease (lpd) were found in mice tra nsplanted with unfractionated PBL and CD8- or CD14-depleted PBL, and in mic e treated with OKT3 at distance from PBL transfer. Animals xenografted with CD3- or CD4-depleted PBL, or treated at transplantation time with OKT3, ha d very low levels of human Ig and did not develop lpd. PBL engraftment was minimal or absent in these animals, as determined by immunohistochemistry, dot-blot, and RT-PCR analyses. These results demonstrate that the presence of donor CD4(+) T lymphocytes at transplantation time is necessary for obse rving human PBL engraftment into SCID mice, an essential condition for huma n Ig production and lpd development. (C) 2001 Academic Press.