T-cell differentiation of human and non-human primate CD34(+) hematopoietic progenitor cells using porcine thymic stroma

Transplantation of swine thymic tissue has been proposed as an approach to reconstitute the immune system of HIV-infected individuals. This is an attr active strategy because miniature swine are readily available as donors and porcine tissue is resistant to infection with HIV-1. Demonstration that po rcine thymus tissue supports primate T-cell differentiation is critical to the ultimate utility of this approach. Using a thymic stroma culture system we have previously described [Rosenzweig M, Marks DF, Zhu H et al. In vitr o T lymphopoiesis of human and rhesus CD34+ progenitor cells. Blood 1996; 8 7: 4040], we demonstrate that porcine thymus tissue is able to promote the in vitro T-lymphocyte differentiation of both human and non-human primate h ematopoietic progenitor cells. CD34(+) hematopoietic progenitors differenti ated into both double positive (CD4(+)CD8(+)) and single positive thymocyte s expressing CD4 or CD8 alone. A polyclonal T-cell repertoire was evident. In addition, the T cells responded appropriately to mitogen and were permis sive to infection with simian immunodeficiency virus (SIV). These data demo nstrate the ability of porcine thymus to support T-cell differentiation of both human and non-human hematopoietic progenitor cells and support in vivo studies of transplantation of swine thymic tissue as a strategy for immune reconstitution in AIDS.