Human antibodies isolated from plasma by affinity chromatography increase the coxsackievirus B4-induced synthesis of interferon-alpha by human peripheral blood mononuclear cells in vitro

Coxsackievirus B4 (CVB4) can be found in circulating blood of patients; how ever, the interaction of CVB4 with peripheral blood mononuclear cells (PBMC s) is poorly understood. CVB4 induced low levels of IFN-alpha synthesis in PBMCs from healthy donors. In contrast, preincubation of infectious CVB4 wi th plasma from these donors containing anti-CVB4 antibodies strongly enhanc ed the synthesis of IFN-alpha, IgG obtained from plasma by chromatography f ormed immune complexes with CVB4 and increased significantly the CVB4-induc ed production of IFN-alpha by PBMCs. These antibodies did not have a neutra lizing effect on CVB4 infection of Hep-2 cells. The role of CVB and adenovi rus receptor (CAR), Fc gamma RII and Fc gamma RIII in the increased synthes is of IFN-alpha induced by CVB4 preincubated with IgG was shown by inhibiti on with specific antibodies. The major interferon-alpha -producing cells in response to CVB4-IgG complexes were CD14(+) cells and monocyte-enriched PB MCs. With the latter, detection of IFN-alpha by immunostaining was positive whereas in monocyte-depleted PBMCs it was not. This study shows that CVB4- induced synthesis of IFN-alpha by PBMCs can be enhanced by an antibody-depe ndent mechanism through interactions between the virus, nonneutralizing ant ivirus antibodies, Fc gamma RII and III and CAR.