INITIAL LENTIVIRUS HOST INTERACTIONS WITHIN LYMPH-NODES - A STUDY OF MAEDI-VISNA VIRUS-INFECTION IN SHEEP

Reactive changes occurring within lymph nodes draining the subcutaneou s site of acute infection with maedi-visna virus (MVV) were studied, a nd the appearance of infected cells correlated with the immune respons e. Cells infected with virus were detected in the node by cocultivatio n from day 4 postinfection (p.i.), with maximum numbers being seen bet ween days 7 and 14, but even then infected cells were rare, with a max imum frequency of 23 50% tissue culture infective doses (TCID50) in 10 (6) lymph node cells. At later times, infected cells were still detect ed, but their numbers fell to 1 to 2 TCID50 per 10(6) cells. Virus-spe cific CD8(+) cytotoxic T-cell precursors (CTLp) were isolated from inf ected nodes from day 10 p.i. onwards, and T-cell proliferative respons es to MW were first detected on day 7 and consistently detected after day 18. Histological analysis showed a vigorous immune response in the node. There was a marked blast reaction in the T-cell-rich zones, whi ch was greatest at the time when the number of virally infected cells was at its height. At this stage, large numbers of plasma cells were s een in the medullary cords, indicating that extensive T-cell-dependent B-cell activation was occurring in the T-cell-rich zones. Germinal ce nters were prominent shortly after the onset of the T-zone response an d were still present at 40 days p.i. Phenotype studies of isolated lym ph node cells failed to detect major changes in the proportion or phen otype of macrophages, CD1(+) interdigitating cells, and CD4(+) or CD8( +) T cells despite the fact that CD8(+) lymphoblasts form a major popu lation leaving the node in efferent lymph. This suggests that there is a balanced increase in the number of all cell types in response to th e virus within the node and selective migration of CD8(+) lymphoblasts containing virus-specific CTLp from the node. Virus-specific immune r esponses are therefore present within the node when infectious virus i solation is maximal, but cellular immunity may act to control the leve l of infection from day 18 onwards.