The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.
Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that tumor necrosis factor (TNF)-α-producing CD8(+) T cells contribute significantly to chlamydial upper genital tract pathology in female mice. In addition, we observed that minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein the CD8(+) T-cell repertoire is restricted to recognition of the ovalbumin peptide Ova(257-264), suggesting that non-Chlamydia-specific CD8(+) T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen-specific CD8(+) T cells mediate chlamydial pathology. Groups of wild-type (WT) C57BL/6J, OT-1 mice, and OT-1 mice replete with WT CD8(+) T cells (1 × 10(6) cells per mouse intravenously) were infected intravaginally with C. muridarum (5 × 10(4) IFU/mouse). Serum total anti-Chlamydia antibody and total splenic anti-Chlamydia interferon (IFN)-γ and TNF-α responses were comparable among the three groups of animals. However, Chlamydia-specific IFN-γ and TNF-α production from purified splenic CD8(+) T cells of OT-1 mice was minimal, whereas responses in OT-1 mice replete with WT CD8(+) T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT-1 mice but reverted to WT levels in OT-1 mice replete with WT CD8(+) T cells. Collectively, these results demonstrate that Chlamydia-specific CD8(+) T cells contribute significantly to upper genital tract pathology.
Department of Pathology, Midwestern University, Downers Grove, IL, USA.|Department of Biomedical Sciences, Midwestern University, Downers Grove, IL, USA.
Kelly R
KR
Vlcek
Department of Pathology, Midwestern University, Downers Grove, IL, USA.
Weidang
W
Li
Department of Pathology, Midwestern University, Downers Grove, IL, USA.
Srikanth
S
Manam
Department of Microbiology and Immunology, Midwestern University, Downers Grove, IL, USA.
Brian
B
Zanotti
Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Bruce J
BJ
Nicholson
Department of Microbiology and Immunology, Midwestern University, Downers Grove, IL, USA.
Kyle H
KH
Ramsey
Department of Pathology, Midwestern University, Downers Grove, IL, USA.
Ashlesh K
AK
Murthy
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000382:microbiology; D007371:Interferon-gamma / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000907:Antibodies, Bacterial; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D010047:Ovalbumin