Allergen-dependent induction of interleukin-4 synthesis in vivo

The ability of freshly derived T cells to produce interleukin-4 (IL-4) remains controversial. Many groups report that freshly derived antigen-, allogen- or mitogen-activated CD4 T cells produce almost exclusively IL-2, acquiring the capacity to produce a spectrum of cytokines following culture, rest and restimulation. In contrast, it is demonstrated here that in vivo exposure to protein allergens induces rapid, co-ordinate activation of IL-4 and interferon-gamma (IFN-gamma) gene expression. Overnight culture of spleen cells obtained from mice immunized with ovalbumin (OVA) or ragweed extract (RAG) in alum adjuvant elicits strong IL-2 and IL-4 responses within 14 hr of culture. T cells from mice immunized with allergen in complete Freund's adjuvant (CFA) generate strong IL-2 and IFN-gamma production, but virtually no IL-4, while unimmunized mice do not respond detectably to allergen in vitro (< 1 U). Unlike the differential pattern of cytokine synthesis observed following antigen-specific in vitro restimulation, cultures derived from naive and allergen-primed animals yield virtually equivalent IL-4, IL-2 and IFN-gamma synthesis upon polyclonal restimulation with anti-CD3 mAb 145-2C11 or concanavalin A (Con A), a finding which underlines the importance of the experimental conditions selected for in vitro analysis of in vivo cytokine gene expression. Collectively, the results indicate that the mode of immunization is critical to the pattern of cytokine response elicited and consequently to the type of antibody response which develops.(ABSTRACT TRUNCATED AT 250 WORDS)