Effects of Adoptive Immune Transfers on Murine Leukemia Virus-Infection of Rats

Abstract

In a rat model, we have investigated the effects of adoptively transferred virus-specific immune cells on an established retroviral infection of various organs. The experimental design required inoculation of neonatal Fisher rats with a molecular clone of Friend murine leukemia virus (F-MuLV; FB29) which resulted in virus-specific immunotolerance, while infection of adult rats lead to a virus-specific humoral and cellular immune response. Adoptive transfer of virus-specific immune cells from immunized to immunotolerant (i.e., neonatally inoculated) rats was performed at around 15 days postpartum, a time when retroviral titers had already reached high levels in serum, spleen, thymus, and central nervous system (CNS). Seven days post-transfer (dpt), virus titers began to decline by 3-5 logs first in sera and at around 11-15 dpt, in spleens and thymi. Approximately 19 days post-transfer viral titers increased again. In the CNS, viral titers appeared not to change after adoptive transfer, although we observed an influx of activated T-cells and natural killer cells (NK-cells), but not of B-cells, into the CNS as well as an upregulation of major histocompatibility complex class I and II molecules between 8 and 21 dpt on both microglia and other brain cells. From these data we conclude that MuLV-infected cells of lymphoid organs can be eliminated by an antiviral immune response. In the CNS, however, most virus-infected cells escaped an immunological attack in spite of the presence of T- and NK-cells and may thus function as a reservoir for MuLVs.