T cell responses in the absence of IFN-gamma exacerbate uterine infection with Chlamydia trachomatis.
Infection with the obligate intracellular bacterium Chlamydia trachomatis is controlled primarily by IFN-gamma and Th1 immunity. In this study, we used cells from a Chlamydia-specific CD4(+) TCR-transgenic mouse to assess the role of IFN-gamma in development of Th1 immunity. We show that secretion of host IFN-gamma or the ability of host cells to respond to secreted IFN-gamma is not required to initiate a Th1 immune response. Additionally, we found that Ag-specific CD4(+) cells that were preskewed toward Th1 confer protection, whereas cells preskewed toward Th2 cause a previously unreported exacerbation of disease leading to higher bacterial load. Chlamydia-specific Th1 cells transferred into an IFN-gamma(-/-) recipient mouse demonstrate protective effects, but the same cells exacerbate bacterial burden when transferred into IFN-gammaR(-/-) mice. Thus, we demonstrate that the secretion of IFN-gamma is necessary for protection against C. trachomatis and that in the absence of host cell IFN-gammaR expression, both Th1 and Th2 cells lead to increased burden of C. trachomatis.
Gondek
David C
DC
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Roan
Nadia R
NR
Starnbach
Michael N
MN
D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis; D005260:Female; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells; D014591:Uterine Diseases / Q000382:microbiology*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor