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 irrad iated Thy-1.2 SCID mice can be used as a model system for thymus homin g and reconstitution after intravenous transfer of rat bone marrow cel ls. Full short-term SCID mouse thymus reconstitutions were obtained us ing a plastic nonadherent low-density rat bone marrow cell subset. Cel l counts and flow cytometric analysis showed that at 3 weeks post-tran sfer, the SCID mouse thymus contained up to 41 x 10(6) Thy-1.1high rat lymphoid cells comprising the expected percentages and distribution o f CD2+, CD5+, CD3+, alphabeta TCR+ and CD4+ CD8+ cells. As seen on cry ostat sections, bone marrow-derived MHC class II+ accessory cells had already developed by 2 weeks post-transfer, preceding the thymocyte ex pansion apparent at 3 weeks. Thus, analysis of the early events of SCI D thymus reconstitution by rat bone marrow cells shows that they close ly resemble those described in congenic animals and points out the tem porally distinct development of dendritic cells and thymocytes. The SC ID mouse-rat chimera model system represents a new in vivo tool for ma nipulating rat T-cell differentiation from bone marrow-resident precur sor cells and in addition supports our previous xenogeneic reconstitut ion studies performed in organ culture.