Interleukin-12 induces interferon-gamma-dependent switching of IgG alloantibody subclass

Interleukin-12 (IL-12) is a key immunoregulatory cytokine which promotes cell-mediated immunity. Its influence on the humoral immune response is less clearly defined. In this study, the effect of systemic IL-12 treatment on the T cell-dependent humoral immune response in the rat was examined using an experimental system in which PVG-RT1u congenic rats were immunized with class I Aa alloantigen in the form of a blood transfusion from the recombinant PVG.R8 rat strain. Administration of IL-12 following allo-immunization augmented the humoral immune response as determined by increased levels of cytotoxic anticlass I major histocompatibility complex antibodies. However, the effect of IL-12 on individual IgG isotypes was highly selective. Levels of allospecific antibodies of the IgG2b and IgG2c subclasses were markedly increased, whereas IgG1 alloantibody levels were profoundly reduced. The observed alterations in alloantibody response were dependent, in large part, on the stimulatory effect of IL-12 on interferon (IFN)-gamma production by T lymphocytes and natural killer cells, since they were abrogated by co-administration of neutralizing anti-IFN-gamma monoclonal antibody following alloantigen immunization.