Interleukin‐12 acts as an adjuvant for humoral immunity through interferon‐γ‐dependent and ‐independent mechanisms

Abstract

Interleukin-12 (IL-12) is a pivotal cytokine that has dramatic effects on cell-mediated immunity. It is now becoming increasingly recognized that IL-12 also strongly controls humoral immunity. We have investigated the mechanism by which IL-12 induces alterations in antibody isotype expression by determining the influence of IL-12 on in vitro immunoglobulin (Ig) production in polyclonally activated murine spleen cell cultures. Cells exposed to IL-12 plus lipopolysaccharide or anti-CD40 monoclonal antibody showed dramatically elevated IgG2a and suppressed IgG1 production compared to cells cultured in the absence of IL-12. IL-12 treatment of spleen cell cultures induced expression of gamma2a germ-line transcripts, consistent with initiation of switch recombination to IgG2a. In addition, exposure of limiting dilution cultures to IL-12 increased IgG2a+ cell precursor frequency. All of the above results were dependent on interferon-gamma (IFN-gamma). However, in the absence of IFN-gamma, IL-12 still had significant effects on Ig secretion. Specifically, IL-12 enhanced IgG1 and IgG2b anti-DNP antibody levels in mice containing specific disruptions in the IFN-gamma gene. Our results suggest that IL-12 induces T helper type 1 and natural killer cells to secrete large amounts of IFN-gamma which then causes B cells to switch to IgG2a and IgG3 production. In addition, IL-12 has direct or indirect effects on B cells that are independent of IFN-gamma. The IFN-gamma-independent effects may include enhancement of Ig expression by post-switched cells.

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

“…We (15)(16)(17) and others (18 -22) have demonstrated the effectiveness of IL-12 as an adjuvant for humoral immunity in adult animals. In addition, we have found that neonatal animals have reduced IL-12 expression in the periphery and that IL-12 delivered at birth can serve as an adjuvant to induce a Th1-like cytokine response and cause priming for enhanced Ab responses to DNP-OVA and hen eggwhite lysozyme (HEL) 3 (23).…”

“…IL-12 is a pivotal cytokine that regulates the biological functions of T cells and NK cells and enhances the production of IFN-␥ and other cytokines (13,14). In addition, IFN-␥ stimulates production of opsonizing Abs such as IgG2a (15,17,31). In the present study, we found that coadministration of IL-12 and influenza vaccine at birth resulted in significant increases in neonatal IFN-␥ mRNA levels.…”

Early Control of Mycobacterium tuberculosis Infection Requiresil12rb1Expression byrag1-Dependent Lineages

“…The cumulative data from both CD4 ϩ and CD8 ϩ T cells are shown in Fig. 10M to N [42,43], thrombocytes [9], mast cells [75], basophils [60], neutrophils [44], eosinophils [40], macrophages [58], and dendritic cells [33]) as well as lymphoid progenitors (NK-cells ( [25], NK T cells [73], B cells [39], ␥␦-T cells [71], CD4…”

IL-12 as an adjuvant for the enhancement of protective humoral immunity

“…It has been found that the inclusion of IL-12 during intranasal vaccination induces significant levels of both pulmonary IgG and IgA antibodies that are not expressed after exposure to vaccine alone. These increases are partially IFN-g dependent and IFN-g independent [28,29]. In experiments with influenza virus infection, it was found that all mice given only phosphate buffered saline before viral challenge succumbed to influenza, and that intranasal immunization with influenza subunit vaccine alone provided only partial protection.…”