title: Differential activation of Brucella-reactive CD4+ T cells by Brucella infection or immunization with antigenic extracts.
abstract: In order to induce acquired cellular resistance to facultative bacterial pathogens, infection with live organisms is required. We have previously demonstrated that spleen cells from Brucella-infected mice produced gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in response to Brucella antigens in vitro, while spleen cells from mice immunized with soluble Brucella proteins (SBP) produced substantial amounts of IL-2 but no detectable amount of IFN-gamma. In this study, we further analyzed the response of T cells from Brucella-infected mice and SBP-immunized mice and demonstrated that CD4(+)-enriched cells from SBP-immunized mice also produced significant amounts of IL-4, which was not detected in bulk cultures of spleen cells from infected mice. Limiting dilution analysis showed that infection resulted in a higher precursor frequency of IFN-gamma-producing CD4+ T cells and a lower precursor frequency of IL-4-producing CD4+ T cells, while immunization with SBP resulted in a higher precursor frequency of IL-4-producing cells and a very low frequency of IFN-gamma-producing cells. The precursor frequencies of IL-2-producing cells for the two groups were similar. Furthermore, IFN-gamma-producing CD4+ T cells from infected donor mice were capable of mediating resistance against challenge infection in recipient mice, but IL-4-producing CD4+ T cells from immunized mice failed to do so. These results indicate that the form of antigen has a profound influence on the outcome of the immune response. The results are discussed in light of the supposed dichotomy between Th1 and Th2 cytokine responses.
authors.affiliation: Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhan
authors.forename: A
authors.initials: A
authors.lastname: Kelso
authors.forename: C
authors.initials: C
authors.lastname: Cheers
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D002004:Brucella Vaccine / Q000276:immunology* / Q000627:therapeutic use; D002003:Brucella abortus / Q000276:immunology; D002006:Brucellosis / Q000276:immunology* / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D002004:Brucella Vaccine; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma