Virus-specific cellular blastogenesis and interleukin-2 production in swine after recovery from African swine fever

Animals recovered from viral diseases represent an important model to study the host cellular and humoral immune responses to the etiologic agents. This is particularly important for African swine fever virus (ASFV) infections in which antibodies have little or no virus-neutralizing effect. Pigs surviving experimental infection with the naturally occurring low-virulent, nonhemadsorbing ASFV/NH/P68 (NHV) isolate did, however, exhibit virus-specific T-cell activities, as measured by a variety of assays. A strong virus-induced, antigen-specific blastogenic response was observed only with blood mononuclear cells (BMC) from ASF-recovered swine, whereas cells from recovered and naive swine responded similarly to the mitogens concanavalin A and phytohemagglutinin. The ASFV-induced blastogenesis was dependent on virus dose and on the presence of adherent cells. Blood mononuclear cells cultured with antigenically related hemadsorbing ASFV isolates of different virulence characteristics, the highly virulent L60 isolate and moderately virulent DRII isolate, exhibited a similar magnitude of blastogenesis to cells infected with the low-virulent NHV isolate. Virus-infected cells proved to be an efficient inducer of interleukin-2 (IL-2) activity to cells from recovered swine, but not from naive swine, whereas T-cell-specific lectins induced production of similar amounts of IL-2 activity from cells of naive and recovered swine. Correlated with the appearance of virus-induced IL-2 activity in the culture supernatant was the induction of promiscuous killing in cells exposed to prolonged (7 days) virus stimulation. This lymphokine-activated killing could be induced experimentally early in the virus stimulatory process (3 days) by the addition of exogenous lymphokines to the cultures. It was concluded that swine inoculated with low-virulent ASFV isolates are a useful model for identifying and characterizing ASFV immune mechanisms in vitro. Furthermore, this ASFV model implicates lymphokines as inducers of nonspecific cell-mediated immunity; in fact, lymphokine-activated killer type responses may contribute to recovery from this viral infection. More important, ASFV-specific blastogenic and cytotoxic T-cells are prime candidates for the cells inducing and/or conferring protective immunity against challenge ASFV infection.