Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

Abstract

Immunosuppressive mediators in tuberculosis pleurisy (pleural fluid (PF)) are associated with the course of disease, but they remain poorly defined. To study the local immune status of patients with tuberculosis pleurisy, we examined the effect of PF on the functions of T cells and the differentiation of Th1 cells. PF could inhibit the ability of T cells to produce cytokines. However, tumor-necrosis factor (TNF)-a derived from non-T cells was not impaired. Further analysis indicated that cell activation and cell cycle progression were also suppressed. Moreover, PF could inhibit Th1 cell differentiation. Importantly, we found that inhibitors of indoleamine 2,3-dioxygenase (IDO) and adenosine and neutralizing antibodies against IL-10 and transforming growth factor (TGF)-b could reverse cytokine production, suggesting that IDO, adenosine, IL-10 and Transforming growth factor-b1 in PF might take part in impairing T-cell functions. Taken together, our data demonstrate for the first time that several immunopathological factors participate in the downregulation of T-cell functions in local PF.

Biological functions of Mycobacterium tuberculosis-specific CD4+T cells were impaired by tuberculosis pleural fluid

“…Other investigators have observed a similar immune suppressed status in patients infected with influenza [36,37] or the measles virus [38,39]. Our preliminary research indicated that PF could inhibit the functions of T cells from normal donors and the differentiation process of Th1 cells [28]. Consistent with these findings, our observation provided the immunological data supporting the idea that PF could deregulate CD4 + T cells mediated anti-M. tuberculosis response locally.…”

“…Whether the microenvironment is beneficial or harmful to local immune response correlates with the presentation and outcome in tuberculosis pleurisy. Our preliminary studies have demonstrated that PF could lead to the dysfunction of T cells isolated from normal donors and inhibition of the differentiation process and functions of Th1 cells [28]. But detailed functional analysis of antigen-specific CD4 + T cells linked with their local milieu has not been reported and required to be further analyzed.…”

Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis

“…Local immune status in the pleural fluid in TB pleurisy has been shown to be immunologically downregulated. In this regard, Li et al demonstrated that an inhibitor of IDO restored decreased T-cell-derived cytokine production in the pleural fluid of patients with TB pleurisy, suggesting that IDO is responsible for the impairment of T-cell functions in TB pleurisy (10). Collectively, these data imply that IDO activity is involved in the immunological processes of TB through its immunosuppressive effect.…”

A diagnostic algorithm for tuberculous pleurisy using the ELISPOT assay on peripheral blood and pleural effusion

“…Li et al showed that the microenvironment of pleural fluid itself inhibited the production of M. tuberculosis-specific cytokines in a dose-dependent manner and suppressed the activation of M. tuberculosis-specific CD4 þ T cells. [28,29] Therefore, an immunosuppressive effect of pleural fluid could have contributed to the negative results in the PE-MC ELISPOT assay in TB pleurisy patients.…”