Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis.

BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

PD-1 analysis on CD28(-) CD27(-) CD4 T cells allows stimulation-independent assessment of CMV viremic episodes in transplant recipients.

Expression of the inhibitory receptor programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific CD4 T cells defines a phenotype associated with CMV viremia in transplant recipients. Moreover, CD28(-) CD27(-) double negativity is known as a typical phenotype of CMV-specific CD4 T cells. Therefore, the co-expression of inhibitory receptors on CD28(-) CD27(-) CD4 T cells was assessed as a rapid, stimulation-independent parameter for monitoring CMV complications after transplantation. Ninety-three controls, 67 hemodialysis patients and 81 renal transplant recipients were recruited in a cross-sectional and longitudinal manner. CMV-specific CD4 T cell levels quantified after stimulation were compared to levels of CD28(-) CD27(-) CD4 T cells. PD-1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression on CD28(-) CD27(-) CD4 T cells were related to viremia. A percentage of ≥0.44% CD28(-) CD27(-) CD4 T cells defined CMV seropositivity (93.3% sensitivity, 97.1% specificity), and their frequencies correlated strongly with CMV-specific CD4 T cell levels after stimulation (r = 0.73, p < 0.0001). Highest PD-1 expression levels on CD28(-) CD27(-) CD4 T cells were observed in patients with primary CMV viremia and reactivation (p < 0.0001), whereas CTLA-4 expression was only elevated during primary CMV viremia (p < 0.05). Longitudinal analysis showed a significant increase in PD-1 expression in relation to viremia (p < 0.001), whereas changes in nonviremic patients were nonsignificant. In conclusion, increased PD-1 expression on CD28(-) CD27(-) CD4 T cells correlates with CMV viremia in transplant recipients and may serve as a specific, stimulation-independent parameter to guide duration of antiviral therapy.