Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis.

ABSTRACT: Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States. Repeated infections with C. trachomatis lead to serious sequelae, such as infertility. It is unclear why the adaptive immune system, specifically the CD8(+) T cell response, is unable to protect against subsequent C. trachomatis infections. In this article, we characterize the mucosal CD8(+) T cell response to C. trachomatis in the murine genital tract. We demonstrate that the immunoinhibitory ligand, PD-L1, contributes to the defective CD8(+) T cell response. Deletion or inhibition of PD-L1 restores the CD8(+) T cell response and enhances C. trachomatis clearance.

SUBMITTER: Fankhauser SC

PROVIDER: S-EPMC3921669 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

PD-L1 limits the mucosal CD8+ T cell response to Chlamydia trachomatis.

Fankhauser Sarah C SC Starnbach Michael N MN

Journal of immunology (Baltimore, Md. : 1950) 20131218 3

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease in the United States. Repeated infections with C. trachomatis lead to serious sequelae, such as infertility. It is unclear why the adaptive immune system, specifically the CD8(+) T cell response, is unable to protect against subsequent C. trachomatis infections. In this article, we characterize the mucosal CD8(+) T cell response to C. trachomatis in the murine genital tract. We demonstrate that the immunoin ...[more]

PMID: 24353266

Similar Datasets

Chlamydia trachomatis L1/224

Project description:Chlamydia trachomatis L1/224 genome sequencing

| PRJEA71103 | ENA

Chlamydia trachomatis L1/115

Project description:Chlamydia trachomatis L1/115 genome sequencing

| PRJEA71101 | ENA

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

Project description:PurposeTo investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).Cases and methodsNinety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).ResultsAfter CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.ConclusionsCHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.

| S-EPMC7862737 | biostudies-literature

Lactobacillus plantarum producing a Chlamydia trachomatis antigen induces a specific IgA response after mucosal booster immunization.

Project description:Mucosal immunity is important for the protection against a wide variety of pathogens. Traditional vaccines administered via parenteral routes induce strong systemic immunity, but they often fail to generate mucosal IgA. In contrast, bacteria-based vaccines comprise an appealing strategy for antigen delivery to mucosal sites. Vaginal infection with Chlamydia trachomatis can develop into upper genital tract infections that can lead to infertility. Therefore, the development of an effective vaccine against Chlamydia is a high priority. In the present study, we have explored the use of a common lactic acid bacterium, Lactobacillus plantarum, as a vector for delivery of a C. trachomatis antigen to mucosal sites. The antigen, referred as Hirep2 (H2), was anchored to the surface of L. plantarum cells using an N-terminal lipoprotein anchor. After characterization, the constructed strain was used as an immunogenic agent in mice. We explored a heterologous prime-boost strategy, consisting of subcutaneous priming with soluble H2 antigen co-administered with CAF01 adjuvant, followed by an intranasal boost with H2-displaying L. plantarum. The results show that, when used as a booster, the recombinant L. plantarum strain was able to evoke cellular responses. Most importantly, booster immunization with the Lactobacillus-based vaccine induced generation of antigen-specific IgA in the vaginal cavity.

| S-EPMC5415134 | biostudies-literature

Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.

Project description:CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy. Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)). ITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ TRM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion. Our analyses indeed demonstrate that the presence of CD103+ CD8+ TRM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.

| S-EPMC8032254 | biostudies-literature

Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma.

Project description:Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host's antigens, but they become progressively exhausted or deleted. These cells express the negative immunoregulatory checkpoint programmed cell death protein 1 (PD-1) which impairs T cell receptor signaling by blocking the CD28 positive co-stimulatory signal. The pool of CD8 cells sensitive to anti-PD-1/PD-L1 treatment is the PD-1dim memory-like precursor pool that gives rise to the effector subset involved in HCC control. Due to the epigenetic imprints that are transmitted to the next generation, the effect of PD-1 blockade is transient, and repeated treatments lead to tumor resistance. During long-lasting disease, besides the TCR signaling impairment, T cells develop other failures that should be also set-up to increase T cell reactivity. Therefore, several PD-1 blockade-based combinatory therapies are currently under investigation such as adding antiangiogenics, anti-TGFβ1, blockade of other negative immune checkpoints, or increasing HCC antigen presentation. The effect of these combinations on CD8+ T cells is discussed in this review.

| S-EPMC8073815 | biostudies-literature

Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function.

Project description:The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells. PD-1 is highly expressed on effector populations, including T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells, which reside in germinal centers. We also show that DC PD-L1 is essential for limiting Tfh and Tfr cell differentiation. In addition, we find that PD-1 suppresses Tfh cell differentiation and help for Ig class switching, even in the presence of wild-type Tfr cells. Our work points to critical roles for PD-L1 expressed on DCs in mediating PD-1 functions.

| S-EPMC6054131 | biostudies-literature

Utility of PD-L1 immunohistochemistry assays for predicting PD-1/PD-L1 inhibitor response.

Project description:We have seen a notable increase in the application of PD-1/PD-L1 inhibitors for the treatment of several solid and hematogenous malignancies including metastatic melanoma, non-small-cell lung cancer and lymphoma to name a few. The need for biomarkers for identification of a suitable patient population for this type of therapy is now pressing. While specific biomarker assays have been developed for these checkpoint inhibitors based on their respective epitopes, the available studies suggested the clinical utility of these biomarker assays is for response stratification and not patient selection. Further improvement in assay development is needed to utilize this type of assay in identification of ideal patient population for this therapy.

| S-EPMC5353958 | biostudies-other

Polarized Cell Division of Chlamydia trachomatis.

Project description:Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the leading bacterial cause of sexually transmitted infections and trachoma, lacks FtsZ, it has been assumed to divide by binary fission. We show here that Chlamydia divides by a polarized cell division process similar to the budding process of a subset of the Planctomycetes that also lack FtsZ. Prior to cell division, the major outer-membrane protein of Chlamydia is restricted to one pole of the cell, and the nascent daughter cell emerges from this pole by an asymmetric expansion of the membrane. Components of the chlamydial cell division machinery accumulate at the site of polar growth prior to the initiation of asymmetric membrane expansion and inhibitors that disrupt the polarity of C. trachomatis prevent cell division. The polarized cell division of C. trachomatis is the result of the unipolar growth and FtsZ-independent fission of this coccoid organism. This mechanism of cell division has not been documented in other human bacterial pathogens suggesting the potential for developing Chlamydia-specific therapeutic treatments.

| S-EPMC4978491 | biostudies-literature

Chlamydia trachomatis L1/440/LN

Project description:Chlamydia trachomatis L1/440/LN genome sequencing

| PRJEA71099 | ENA