Association of CD80 and CD86 Expression Levels with Disease Status of Visna/Maedi Virus Infected Sheep

Abstract

In small ruminant lentivirus infections, cellular immune responses are diminished in clinically affected animals. The underlying mechanisms for this are unknown. In this study, we tested the hypothesis that alterations in expression of the co-stimulatory molecules B7-1 and B7-2 are involved in infections with Visna/Maedi virus (VMV), the prototype lentivirus of sheep. We studied B7 expression levels ex vivo in peripheral blood mononuclear cells (PBMCs), determining B7 RNA levels by real time reverse transcriptase polymerase chain reaction in asymptomatic as well as clinically affected VMV-seropositive sheep. The levels of both B7 molecules were increased in VMV-seropositive asymptomatic sheep. However, in VMV clinically affected sheep, the level of CD80 (but not CD86) was low compared with the level in uninfected sheep (p < 0.05). CD80 and CD86 RNA levels were associated with the ability of PBMCs to respond to VMV gag antigens (p14, p17, and p25) by proliferation, with most seropositive asymptomatic sheep showing positive proliferative responses but clinically affected sheep showing no response. The response to p25 in clinically affected animals was increased by the addition of interleukin-2 to the cultures. Decreased recall responses to unrelated antigens (assessed by production of interferon-gamma) were also found in clinically affected sheep. Thus, among seropositive sheep, decreased B7-1 (CD80) RNA levels and diminished antigen-specific cellular immune responses in PBMCs point to a VMV disease status, whereas increased CD80 and CD86 levels and augmented cellular responses are linked to asymptomatic infection.