Chlamydia muridarumT-Cell Antigens Formulated with the Adjuvant DDA/TDB Induce Immunity against Infection That Correlates with a High Frequency of Gamma Interferon (IFN-γ)/Tumor Necrosis Factor Alpha and IFN-γ/Interleukin-17 Double-Positive CD4⁺T Cells

Abstract

Major impediments to developing a Chlamydia vaccine lie in identifying immunologically relevant T-cell antigens and delivery in a manner to stimulate protective immunity. Using an immunoproteomic approach, we previously identified three immunodominant Chlamydia T-cell antigens (PmpG-1, PmpE/F-2, and RplF). Because RplF has high homology to a human ortholog, it may not be suitable for human vaccine development. Therefore, in this study, we evaluated protection against Chlamydia infection in the genital tract in C57BL/6 mice immunized with Chlamydia-specific membrane proteins PmpG-1, PmpE/F-2, and major outer membrane protein (

Interleukin-17 Contributes to Generation of Th1 Immunity and Neutrophil Recruitment duringChlamydia muridarumGenital Tract Infection but Is Not Required for Macrophage Influx or Normal Resolution of Infection

“…Unfortunately, the intense infiltration of nonneutrophil leukocytes observed in the absence of IFN-␥ prevented adequate assessment of the role of neutrophils or IL-17 in pathology. Because the antibody utilized in these experiments targeted IL-17A, it is possible that the continued presence of IL-17F provided sufficient signaling to result in production of neutrophil-promoting chemokines and neutrophil influx, albeit at reduced levels, which could explain the absence of an effect on pathology in the ϩ T cells (45). Indeed, our data reveal that removal of IL-17 blunts Th1 priming during genital tract infection.…”

“…The reduction in T cell numbers detected at day 20 compared to day 7 is likely due to reduced bacterial burden and reduced antigen stimulation related to in vivo clearance of infection. It is possible that a percentage of cells produced both IFN-␥ and IL-17 (45). Experiments were then conducted to examine the role of the IL-17/Th17 response during genital tract chlamydial infection.…”

PmpG 303-311 , a Protective Vaccine Epitope That Elicits Persistent Cellular Immune Responses in Chlamydia muridarum-Immune Mice

“…We previously identified a panel of CD4 and CD8 T cell epitopes by immunoprecipitation of MHC class II and class I molecules from infected C57BL/ 6-derived dendritic cells, eluting the resident peptides, and identifying those peptides using matrix-assisted laser desorption ionizationtime of flight mass spectrometry (MALDI-TOF MS) (14,32). We found that of the identified epitope source proteins, immunization with a PmpG-1 fusion protein, the source protein for the I-A b -presented epitope PmpG 303-311 , provided the greatest protection against C. muridarum infectious challenge in the genital tract (30,31).…”

Th17 cell-Mediated Responses in Type 1 Diabetes Pathogenesis

“…The plasticity of Th17 cells has also been recently demonstrated by several reports that described the existence of a subtype of Th17 cells able to produce both IL-17 and IFN-γ which is named IL-17/IFN-γ double positive T cells or Th17/Th1 cells [20,[58][59][60][61]. It has been shown that Th17-polarizing treatments in the absence of TGF-β induced double-secreting Th17 cells which co-express IL-17 and IFN-γ whereas polarization in the presence of TGF-β induced IL-17 single-secreting Th17 cells [62,63].…”