title: Functional characterization of class Ia- and non-class Ia-restricted Chlamydia-reactive CD8+ T cell responses in humans.
abstract: CD8(+) T cells are a key immune component for the eradication of many intracellular pathogens. This study aims to characterize the human CD8(+) T cell response to naturally processed chlamydial Ags in individuals exposed to the intracellular pathogen Chlamydia trachomatis. By using C. trachomatis-infected autologous dendritic cells (DCs) as stimulators, Chlamydia-reactive CD8(+) T cell responses were detected in all 10 individuals tested. The majority of the Chlamydia-reactive CD8(+) T cells were non-MHC class Ia restricted in all three of the individuals tested. From one donor, three non-class Ia-restricted and two class Ia-restricted Chlamydia-specific CD8(+) T cells were cloned and characterized further. All five T cell clones secreted IFN-gamma in response to autologous DCs infected with viable Chlamydia, but not with DCs pulsed with inactivated chlamydial elementary bodies. MHC class Ia-restricted and non-class Ia-restricted responses were inhibited by DC treatment with a proteasomal inhibitor and an endoplasmic reticulum-Golgi transport inhibitor, suggesting that these T cells recognize a peptide Ag translocated to the host cell cytosol during infection that is processed via the classical class Ia Ag-processing pathway. Even though both restricted and nonrestricted CD8(+) T cells produced IFN-gamma in response to Chlamydia-infected fibroblasts, only the non-class Ia-restricted cells were lytic for these targets. The class Ia-restricted CTLs, however, were capable of cytolysis as measured by redirected killing. Collectively, these data demonstrate that both class Ia-restricted and non-classically restricted CD8(+) T cells are elicited in C. trachomatis-exposed individuals. Their role in host immunity remains to be elucidated.
authors.affiliation: Corixa Corporation, Seattle, WA 98104, USA.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gervassi
authors.forename: Peter
authors.initials: P
authors.lastname: Probst
authors.forename: Walter E
authors.initials: WE
authors.lastname: Stamm
authors.forename: Jeanne
authors.initials: J
authors.lastname: Marrazzo
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Grabstein
authors.forename: Mark R
authors.initials: MR
authors.lastname: Alderson
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000276:immunology*; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma