Henao-Tamayo M, Irwin SM, Shang S, Ordway D, Orme IM. T lymphocyte surface expression of exhaustion markers as biomarkers of the efficacy of chemotherapy for tuberculosis. Tuberculosis (Edinb). 2011 Apr 27. [Epub ahead of print]
In this week’s article, potential cellular biomarkers are explored in the mouse model with three potential markers: PD-1 (program death-1) and TIM-3 (T cell immunoglobulin mucin-3) on CD8 T cells and KIRG-1 (killer cell lectin-like receptor G1) on both CD4 and CD8 T cells. The search for validated biomarkers that can predict treatment success has been a difficult one. The focus of much of the research on biomarkers has been on serum markers, because of practical reasons and considerations of use in resource-limited settings. Henao-Tamayo, et al., took a different focus looking at markers on the surface of lung T cells. Key points from the article include:
- Flow cytometry analysis was used to look at t-cell populations in the lungs of C57BL/6 mice infected with H37RV and untreated, infected with H37RV and treated with rifampicin and isoniazid, and uninfected.
- In one set of experiments, the markers CD27, PD-1, and Tim-3 on CD8 cells were highly expressed in infected/untreated mice which was in contrast to the decrease in levels of expression with decrease in bacterial load in infected/treated mice. By the end of treatment, the infected/treated mice had expression levels of these markers similar to uninfected mice.
- The authors looked at T cell activation marker KLRG-1 which is found on the surface of T cells. This marker was decreased in expression on both CD4 and CD8 T cells after treatment.
- The results may not be reflected in T cells obtained from the blood but it is worth investigating in the authors’ opinion.
Additional TB R&D News:
Metabolite-enabled eradication of bacterial persisters by aminoglycosides