Gamma interferon production by cytotoxic T lymphocytes is required for resolution of Chlamydia trachomatis infection.
In this study, we used mice in which the gene for gamma interferon (IFN-gamma) has been disrupted (IFN-gamma-/- mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-gamma-/- mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-gamma+/+ control mice. Activated CD8(+) cytotoxic T lymphocytes (CTL) secrete IFN-gamma in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-gamma+/+ CTL lines are transferred into Chlamydia-infected IFN-gamma-/- mice, the transferred CTL cannot overcome the immune defect seen in the IFN-gamma-/- mice. We also show that Chlamydia-specific CTL can be cultured from IFN-gamma-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-gamma-/- CTL into infected IFN-gamma+/+ mice does not reduce the level of infection. These results suggest that IFN-gamma production by CTL is not sufficient to overcome the defect that IFN-gamma-/- mice have in the resolution of Chlamydia infection, yet IFN-gamma production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-gamma+/+ mice.
Departments of Laboratory Medicine and Medicine, University of Washington, Seattle, Washington 98195, USA.
M F
MF
Lampe
C B
CB
Wilson
M J
MJ
Bevan
M N
MN
Starnbach
D016475:3T3 Cells; D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation
D007371:Interferon-gamma