Rat-SCID chimeras: Functional characteristics of the immune system of SCID mice after transplantation of rat fetal hematopoietic cells

Abstract: It has been demonstrated that allogeneic and xenogeneic lymphocytes can survive and expand in severe combined immunodeficiency (SCID) mice, but the T-cell function of the chimeras has not always been tested. The aim of this study was to develop a rat-SCID xenogeneic chimera and to examine the T cell response against RT1-incompatible rat cells. Fetal liver cells (FLC) from Lewis (LEW) rats were injected i.v. into irradiated C.B-17-scid (SCID) mice at a dose of 4×10⁷ cells/mouse. After 4 weeks, FACS analysis of peripheral blood lymphocytes (PBL) with monoclonal antibodies specific for rat lymphocyte subpopulations showed full reconstitution. The mice carried 6.2(±1.6)×10⁶ PBL/ml and 92.5 (±39.5)×10⁶ cells in the spleen. PBL, spleen, and lymph nodes showed distribution of CD4, CD8, and RT1 rat cellular markers similar to that observed in normal rats. Spleen cells from rat-SCID chimeras demonstrated normal proliferative T cell responses to Concanavalin A. Chimeras were primed i.p. with 10⁷ Brown Norway (BN) and ACI rat spleen cells, and the responder spleen cells of these primed chimeras showed specific proliferative responses in mixed lymphocyte culture (MLC) against BN and ACI stimulator lymphoid cells, respectively. Specific proliferative responses of rat-SCID chimeras were higher against ACI than BN stimulators. These MLCs also expanded cytolytic T lymphocytes that lysed ⁵¹Cr labeled BN and ACI targets at levels up to 50–90%, respectively. In conclusion, rat FLC injected into SCID mice differentiate and repopulate the immune system as well as function in generating alloantigen-specific cytolytic and helper T cells.