Slide Presentations: Tuesday, October 25, 2011 |

Restoration of Effector T Cell Response in Human Tuberculosis: Involvement of Treg Cells and PD-1 Pathway in Rescuing IFN-γ Production by Antigen Reactive T Cells FREE TO VIEW

Dipendra Mitra, PhD; Amar Singh, PhD; Aparajita Bindu Dey, MD; Anant Mohan, MD
Chest. 2011;140(4_MeetingAbstracts):1016A. doi:10.1378/chest.1117807
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PURPOSE: Bulk T cell response at the pathologic site(s) human tuberculosis depends on the proportional recruitment of various fine T cell subsets including effector and FoxP3+ regulatory T cells (Treg). We previously showed the crucial role of preferential accumulation of Treg cells in causing interleukin-10 mediated local immune deficit and thus disease dissemination (Mitra et al, AJRCCM, 2009). However, little is known on the programmed death receptor (PD-1) expression on Treg cells and its role in suppression of effector T cells in tuberculosis. Therefore, we investigated the role of PD-1/PD-L1 pathways in Treg mediated suppression of Mycobacterium tuberculosis (Mtb.) specific T cell response among tuberculosis patients.

METHODS: Peripheral blood of 21 treatment naÏve patients of pulmonary tuberculosis and 16 healthy controls were studied for the expression of theses molecules (PD-1/PD-Ls) on Treg cells and their influence in dampening the effector T cell function. Multicolor Flow cytometry and ELISA were employed.

RESULTS: The study revealed significant enrichment of FoxP3+ Treg cells among tuberculosis patients and they proliferated after in vitro antigen stimulation, suggesting their antigen driven expansion. Treg cell enrichment tightly correlated with increased IL-10 levels and decreased IFN-γ/IL-4 ratio among these patients. We observed higher expression of PD-1 and PD-L1 CD4+Foxp3+ Treg cells. Blocking the PD-1/PD-L1 pathway significantly enhanced the interferon-γ (IFN-γ) production by the Mtb. antigen reactive T cells.

CONCLUSIONS: Treg cells play critical role in dampening the effector immune response and PD-1/PD-Ls interaction is involved in such suppression of host immunity against Mtb. among patients.

CLINICAL IMPLICATIONS: Targeting Treg cells and PD-1 pathway may rescue the host T cell response for immune based therapies in tuberculosis.

DISCLOSURE: The following authors have nothing to disclose: Dipendra Mitra, Amar Singh, Aparajita Bindu Dey, Anant Mohan

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