The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4+ and CD8+ T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.

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SCID-hu mice with human fetal thymic or lymph node implants were inoculated with the cloned human immunodeficiency virus-1 isolate, HIV-1JR-CSF. In a time- and dose-dependent fashion, viral replication spread within the human lymphoid organs. Combination immunohistochemistry and in situ hybridization revealed only viral RNA transcripts in most infected cells, but some cells had both detectable viral transcripts and viral protein. Infected cells were always more apparent in the medulla than in the cortex of the thymus. These studies demonstrate that an acute infection of human lymphoid organs with HIV-1 can be followed in the SCID-hu mouse.

Cell-free filtrates of x-ray-induced lymphoid tumors of strain C57BL/ Ka mice have elicited, on injection into newborn isologous hosts, a lymphoma incidence of 15 to 19 percent. In control mice of the same subline, the incidence of spontaneous lymphoma is about 1 percent. No leukemogenic activity could be detected in filtrates from thymi harvested at 2 to 32 days following completion of x-ray treatment. Activity was evident at 64 days and was perhaps somewhat greater at 128 days. Serial cell-free passage of filtrates in newborn F(1) hybrid mice resulted in a marked increase in lymphoma incidence (69 percent), coupled with a shortening of the median latency. Supplementary x-irradiation failed to enhance the activity of filtrates after neonatal injection.

The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4+ and CD8+ T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.

Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BH/Ka mice by fractionated X-irradiation or by inoculation of the radiation leukemia virus (RadOV). The cultured cells are lymphoblastic, replicate rapidly in vitro, and are tumorigenic in vivo. The cell surface markers Thy 1, Ly 1, Ly 2,3 and GIX are expressed by the lymphoid tumor cells in the mouse and persist in the corresponding cell lines; expression of the H-2 and TL antigens is greatly reduced during in vitro passage, but is restored on in vivo transplantation. The cell lines derived from RadLV-induced tumors (BL/VL lines) produce a virus population (RadLV/LTC) with the thymotropic and leukemogenic attributes of RadLV. Those derived from radiation-induced, virus-negative lymphomas (BL/RL lines) are initially devoid of MuLV expression, but frequently become spontaneous virus producers during in vitro cultivation.

Radiation leukemia virus, isolated from radiation-induced lymphomas in C57BL/Ka mice and propagated in that strain, is thymotropic and leukemogenic in vivo but replicates poorly, if at all, in mouse and mink fibroblast cultures in vitro. Comparative studies indicate that this naturally occurring virus is distinct from the previously recognized classes of endogenous murine ecotropic and xenotropic C-ype viruses which are capable of replication on fibroblasts (fibrotropic) but are neither thymotropic nor leukemogenic. These studies also demonstrate that a differentiation-specific restriction system governing the replication of the murine ecotropic C-type viruses operates in addition to the previously defined Fv-1 and SRV gene restriction systems. Radiation leukemia virus (RadLV), a naturally occurring murine leukemogenic virus, is recovered from thymic lymphomas induced by x-irradiation in strain C57BL/Ka mice (1, 2). This virus replicates selectively in the host thymus (3, 4). Mice of strain C57BL have also been shown to harbor three classes of endogenous C-type viruses, all of which can be propagated on fibroblastic cells in vitro but differ in host range. They include B-tropic (5, 6), N-tropic (6, 7), and X-tropic viruses (8,9). It is now reported that the thymotropic, leukemogenic particles in RadLV differ at the molecular level, as revealed by their antigenic determinants, from the B, N, and X endogenous viruses and from any combination thereof, and must therefore be recognized as a distinctive subclass of murine ecotropic viruses. MATERIALS AND METHODSMice. C57BL/Ka mice of both sexes, 3-5 weeks of age, were obtained from our own colony. NIH/Swiss mice were kindly provided by Dr.

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