Functional expression of human CD8 in fully reconstituted mice after retroviral-mediated gene transfer of hemopoietic stem cells

Retroviral-mediated gene transfer has been used in an attempt to efficiently and stably express functional cell-surface molecules in lymphoid and myeloid cells. The human CD8 molecule is a T cell-specific surface receptor that is intimately involved in class I MHC-restricted Ag recognition and subsequent T cell activation. After infection with a recombinant, replication-defective retrovirus containing the human CD8α cDNA, bone marrow cells were transplanted into lethally irradiated recipients. The majority of lymphoid and myeloid cells of reconstituted animals expressed high levels of human CD8 for at least 8 months after transplantation. Transfer of bone marrow and spleen cells from these recipients 100 days after transplantation into secondary recipients also resulted in long term expression of CD8 in lymphoid and myeloid cells. CD8 expressed in splenic T cells associated with the lymphoid-specific tyrosine protein kinase p56^lck, participated in T cell activation and conferred an increased xenogeneic response to human MHC class I Ag. Thus, retroviral-mediated gene transfer allows the long term, functional expression of cell-surface molecules in normal murine lymphoid and myeloid cells.