Duration of the foot-and-mouth disease virus antibody response in mice is closely related to the presence of antigen-specific presenting cells

A Wigdorovitz, P Zamorano, FM Fernandez, O Lopez, M Prato-Murphy, C Carrillo, AM Sadir and MV Borca Instituto de Virologia, C.I.C.V., INTA-Castelar, Buenos Aires, Republica Argentina. Natural and experimental hosts infected with foot-and-mouth disease virus (FMDV) develop a long-lasting immune response that is closely related to the presence of anti-FMDV antibodies (Ab). We show here that spleen cells from animals which had been infected 3 or more months previously induced an anti-FMDV-Ab response in untreated animals which lasted more than 210 days after cell transfer. Persistence of infectious virus was excluded since virus isolation or detection of the viral genome by PCR in donor splenocytes were consistently negative. The role of antigen presentation (AP) in this phenomenon was studied in vivo by using irradiated splenocytes from virus-sensitized donor mice. Although these irradiated cells were unable to induce anti-FMDV-Ab in normal or irradiated recipient mice, they elicited a strong secondary reaction in FMDV-pre-sensitized recipients. The presence of AP cells (APC) presenting FMDV epitopes (FMDV/APC) was also analysed in mice sensitized to FMDV in different ways. A close correlation between FMDV/APC and the presence of anti-FMDV-Ab was found in infected mice as well as in mice immunized with different doses of inactivated virus, with or without adjuvants. Experiments in vivo and in vitro showed that the APC activity can be specifically blocked with either anti-MHC class II monoclonal antibody or anti-FMDV antiserum, and is dependent on the presence of T cell function. These results strongly suggest that persistent FMDV/APC are responsible for the existence and maintenance of an anti-virus immune response regardless of the immunization method used.