title: Ontogeny of Th1 memory responses against a Brucella abortus conjugate.
abstract: Protective immune responses to intracellular pathogens such as Brucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but not B. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In 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 levels 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. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-gamma) mRNA. The absence of the early IFN-gamma response in 1-day-old mice may explain their inability to generate 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 antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses.
authors.affiliation: Laboratory of Plasma Derivatives, Division of Hematology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892, USA.
authors.forename: O
authors.initials: O
authors.lastname: Scharf
authors.forename: I
authors.initials: I
authors.lastname: Agranovich
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: N L
authors.initials: NL
authors.lastname: Eller
authors.forename: L
authors.initials: L
authors.lastname: Levy
authors.forename: J
authors.initials: J
authors.lastname: Inman
authors.forename: D E
authors.initials: DE
authors.lastname: Scott
authors.forename: B
authors.initials: B
authors.lastname: Golding
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D006358:Hot Temperature; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D002004:Brucella Vaccine; D016207:Cytokines; D012333:RNA, Messenger; D018074:Vaccines, Conjugate; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin