Functional Characterization of Class Ia- and Non-Class Ia-RestrictedChlamydia-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-γ 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-γ 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.

Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization

“…However, for autologous naive CD4 ϩ or CD8 ϩ T cells, Lactobacillus-activated MDCs did not induce their proliferation or activation. These results may represent a recall response to endogenous lactobacilli or polyclonal T cell activation, as demonstrated previously for Toxoplasma gondii and in Chlamydia trachomatis infection (35)(36)(37).…”

Human CD8+ T Cells Recognize the 60-kDa Cysteine-Rich Outer Membrane Protein fromChlamydia trachomatis

“…Chlamydia-specific CD8 ϩ T cell responses from PBMC were quantified by IFN-␥ ELISPOT as previously described (18). Briefly, CD8…”

“…ϩ T cell clones Chlamydia-reactive CD8 ϩ T cell CD8-30 was cloned by the limiting dilution approach described by Lewinsohn et al (28) and Gervassi et al (18). Briefly, CD8…”

“…We have recently described a method for cloning Chlamydiaspecific human CD8 ϩ T cells using C. trachomatis-infected dendritic cells (DC) (18). Using this approach, the Ag and the restricting allele may reflect more closely the natural CD8 ϩ T cell response in vivo.…”

CD8+ T Cell Protective Immunity against Chlamydia pneumoniae Includes an H2-M3-Restricted Response That Is Largely CD4+ T Cell-Independent

“…That this subset of CD8 ϩ T cells participate in the human host response to intracellular bacteria is suggested by the fact that most M. tuberculosis-specific CD8 ϩ T cells in the peripheral blood of subjects with latent tuberculosis infection are restricted by the human class Ib molecule HLA-E (33,34). Moreover, recent studies in Chlamydia trachomatis-exposed individuals indicate that the majority of Chlamydia-reactive CD8 ϩ T cells recognize infected cells in a nonclassically restricted manner (35,36). Nevertheless, it is uncertain whether MHC class Ib-restricted CD8 ϩ T cells are induced during Cpn infection and whether these T cells contribute to protection.…”