PRECLINICAL ANIMAL MODEL TO ASSESS THE SAFETY OF RETROVIRALLY RESISTANT CELLS

重振HIV感染者免疫系统的诸多策略之一

Of many strategies to revitalize the immune system in HIV infected individuals, the transplant of lymphoid cells resistant to retroviral disease into afflicted individuals is being pursued, in the hope that such cells will mediate anti-retroviral immunity and restore immune responsiveness. However, little is known about qualitative or quantitative factors essential for mediation of resistance. Using a murine model of acquired immunodeficiency induced by retroviruses, we are exploring such parameters by constructing allophenic mice in which one parent is susceptible to MAIDS (murine acquired immunodeficiency syndrome) while the other is resistant. In two different strain combinations in which resistance was predicated on different mechanisms, the presence of substantial, but less than predominant numbers of resistant cells afforded no protection against disease, with such animals developing lymphadenopathy and dying in the same time frame or more rapidly than fully susceptible control mice and with comparable recovery of retroviral species. However, in multiple animals in which the predominant lymphoid population was of the resistant genotype, the animals failed to develop disease, and the level of retroviral species diminished or disappeared. It is thus apparent that there is a critical balance between susceptible and resistant lymphoid cells that determines whether the animals succumb to disease, or achieve long term resistance. We are now assessing what elements of anti-viral immunity are critical for protection in this model. We are constructing allophenic mice in which the resistant strain cells are deficient in interferon gamma, to assess whether this factor is critical for protection and will attempt to construct animals in which the resistant strain cells are deficient in perforin, to assess the role of CTL in this model. Sechler, JMG, Lawler, A., Hartley, JW, Morse, HC,III, and Rosenberg, AS. Induction of MAIDS in Allophenic Mice Generated from Strains Susceptible and Resistant to Disease.