ANALYSIS OF EARLY RECONSTITUTION EVENTS IN THE SCID MOUSE THYMUS FOLLOWING RAT BONE-MARROW CELL TRANSPLANTATION

In this work, we provide comprehensive evidence that sublethally irradiated Thy-1.2 SCID mice can be used as a model system for thymus homing and reconstitution after intravenous transfer of rat bone marrow cells. Full short-term SCID mouse thymus reconstitutions were obtained using a plastic nonadherent low-density rat bone marrow cell subset. Cell counts and flow cytometric analysis showed that at 3 weeks post-transfer, the SCID mouse thymus contained up to 41 x 10(6) Thy-1.1high rat lymphoid cells comprising the expected percentages and distribution of CD2+, CD5+, CD3+, alphabeta TCR+ and CD4+ CD8+ cells. As seen on cryostat sections, bone marrow-derived MHC class II+ accessory cells had already developed by 2 weeks post-transfer, preceding the thymocyte expansion apparent at 3 weeks. Thus, analysis of the early events of SCID thymus reconstitution by rat bone marrow cells shows that they closely resemble those described in congenic animals and points out the temporally distinct development of dendritic cells and thymocytes. The SCID mouse-rat chimera model system represents a new in vivo tool for manipulating rat T-cell differentiation from bone marrow-resident precursor cells and in addition supports our previous xenogeneic reconstitution studies performed in organ culture.