Foxp3+ Regulatory T Cells among Tuberculosis Patients: Impact on Prognosis and Restoration of Antigen Specific IFN-γ Producing T Cells

Abstract

CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB) patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis–specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.

Role of soluble programmed death-1 (sPD-1) and sPD-ligand 1 in patients with cystic echinococcosis

“…No significant effects were measured on IFN-γ or IL-17. These results are consistent with those of previous studies in other diseases (19), suggesting that sPD-L1 inhibits Th1 immune responses and supports the Th2 immune response, resulting in a stronger Th2 immune response.…”

Two Cases of Tuberculosis Manifesting as Cutaneous Solitary Mass in Patients with Adult T-Cell Leukemia/Lymphoma

“…With regard to the relation between Treg cells and TB, one report states that patients with TB have more Treg cells in their peripheral blood compared with healthy controls [12]. Another study demonstrated that Treg-cell-depleted mice infected with TB have a low bacterial load in the lungs after aerosol infection [13].…”

HIV induced suppression of host immunity: relevance to <i>Mycobacterium tuberculosis</i> infections

“…The production of IL-10 was increased among infected individuals and Treg cells are found to be one of the dominant producers of IL-10 [41,42,54,128,[172][173][174] (Figure 3). Increased level of IL-10 producing Treg cells offers a conducive platform form reactivation of latent TB infection and its progression in disseminated form of TB [175][176][177][178]. It is also demonstrated that the blocking of IL-10 with anti-IL-10 Ab restores the effector immune response.…”