title: Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1b on CD8+ T Cells and TNF Receptor Superfamily Member 1a on Non-CD8+ T Cells Contribute Significantly to Upper Genital Tract Pathology Following Chlamydial Infection.
abstract: BACKGROUND
  We demonstrated previously that tumor necrosis factor α (TNF-α)-producing Chlamydia-specific CD8(+) T cells cause oviduct pathological sequelae.
  
  
  METHODS
  In the current study, we used wild-type C57BL/6J (WT) mice with a deficiency in genes encoding TNF receptor superfamily member 1a (TNFR1; TNFR1 knockout [KO] mice), TNF receptor superfamily member 1b (TNFR2; TNFR2 KO mice), and both TNFR1 and TNFR2 (TNFR1/2 double KO [DKO] mice) and mix-match adoptive transfers of CD8(+) T cells to study chlamydial pathogenesis.
  
  
  RESULTS
  TNFR1 KO, TNFR2 KO, and TNFR1/2 DKO mice displayed comparable clearance of primary or secondary genital Chlamydia muridarum infection but significantly reduced oviduct pathology, compared with WT animals. The Chlamydia-specific total cellular cytokine response in splenic and draining lymph nodes and the antibody response in serum were comparable between the WT and KO animals. However, CD8(+) T cells from TNFR2 KO mice displayed significantly reduced activation (CD11a expression and cytokine production), compared with TNFR1 KO or WT animals. Repletion of TNFR2 KO mice with WT CD8(+) T cells but not with TNFR2 KO CD8(+) T cells and repletion of TNFR1 KO mice with either WT or TNFR1 KO CD8(+) T cells restored oviduct pathology to WT levels in both KO groups.
  
  
  CONCLUSIONS
  Collectively, these results demonstrate that TNFR2-bearing CD8(+) T cells and TNFR1-bearing non-CD8(+) T cells contribute significantly to oviduct pathology following genital chlamydial infection.
authors.affiliation: Department of Pathology.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Manam
authors.affiliation: Department of Pathology.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Thomas
authors.affiliation: Department of Pathology.
authors.forename: Weidang
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology.
authors.forename: Allison
authors.initials: A
authors.lastname: Maladore
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Schripsema
authors.affiliation: Department of Microbiology and Immunology, Midwestern University, Downers Grove, Illinois.
authors.forename: Kyle H
authors.initials: KH
authors.lastname: Ramsey
authors.affiliation: Department of Pathology.
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D002690:Chlamydia Infections / Q000473:pathology*; D005260:Female; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis*; D060737:Reproductive Tract Infections / Q000473:pathology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: CD8+ T cells; Chlamydia; TNF receptor 1; TNF receptor 2; genital infection; oviduct pathology