Ontogeny of Th1 memory responses against a Brucella abortus conjugate

Protective immune responses to intracellular pathogens such as Brucella abo rtus are characteristically Th1-like. Recently we demonstrated that heat-ki lled B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKB A-OVA), but not B. abortus alone, can alter the antigen-specific cytokine p rofile from Th2- to Th1-like. In this report we study the ability of a sing le injection of B. abortus to switch a Th2 to a Th1 response in immature mi ce. One-day- and 1-week-old mice were given a single injection of B. abortu s in the absence or presence of OVA, and at maturity mice were challenged w ith an allergenic preparation, OVA with alum (OVA-A). B. abortus given with out OVA did not diminish the subsequent Th2 response in either age group. I n contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E level s after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus or B. a bortus-OVA administration. However, only the 1-week-old mice exhibited incr eased expression of gamma interferon (IFN-gamma) mRNA. The absence of the e arly IFN-gamma response in 1-day-old mice may explain their inability to ge nerate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with ant igen evokes either a Th1- or a Th2-like response which becomes imprinted, s o that subsequent memory responses conform to the original Th bias. This ha s implications for protection against infectious agents and development of allergic responses.