| Title: |
PD-1 Expression on Mycobacterium tuberculosis-Specific CD4 T Cells Is Associated With Bacterial Load in Human Tuberculosis |
| Authors: |
Cheryl L. Day, Deborah A. Abrahams, Rubina Bunjun, Lynnett Stone, Marwou de Kock, Gerhard Walzl, Robert J. Wilkinson, Wendy A. Burgers, Willem A. Hanekom |
| Source: |
Frontiers in Immunology, Vol 9 (2018) |
| Publisher Information: |
Frontiers Media S.A., 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
CD4 T cell, CD8 T cell, tuberculosis, PD-1, IFN-γ, proliferation, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Persistent antigen stimulation in chronic infections has been associated with antigen-specific T cell dysfunction and upregulation of inhibitory receptors, including programmed cell death protein 1 (PD-1). Pulmonary tuberculosis (TB) disease is characterized by high levels of Mycobacterium tuberculosis (Mtb), yet the relationship between bacterial load, PD-1 expression, and Mtb-specific T cell function in human TB has not been well-defined. Using peripheral blood samples from adults with LTBI and with pulmonary TB disease, we tested the hypothesis that PD-1 expression is associated with bacterial load and functional capacity of Mtb-specific T cell responses. We found that PD-1 was expressed at significantly higher levels on Th1 cytokine-producing Mtb-specific CD4 T cells from patients with smear-positive TB, compared with smear-negative TB and LTBI, which decreased after completion of anti-TB treatment. By contrast, expression of PD-1 on Mtb-specific CD8 T cells was significantly lower than on Mtb-specific CD4 T cells and did not differ by Mtb infection and disease status. In vitro stimulation of PBMC with Mtb antigens demonstrated that PD-1 is induced on proliferating Mtb-specific CD4 T cells and that Th1 cytokine production capacity is preferentially maintained within PD-1+ proliferating CD4 T cells, compared with proliferating Mtb-specific CD4 T cells that lack PD-1 expression. Together, these data indicate that expression of PD-1 on Mtb-specific CD4 T cells is indicative of mycobacterial antigen exposure and identifies a population of effector cells with Th1 cytokine production capacity. These studies provide novel insights into the role of the PD-1 pathway in regulating CD4 and CD8 T cell responses in Mtb infection and provide rationale for future studies to evaluate PD-1 expression on antigen-specific CD4 T cells as a potential biomarker for bacterial load and treatment response in human TB. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01995/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2018.01995 |
| Access URL: |
https://doaj.org/article/1ea55180d92c40acade8df0e0220def6 |
| Accession Number: |
edsdoj.1ea55180d92c40acade8df0e0220def6 |
| Database: |
Directory of Open Access Journals |
