Foxp3+ regulatory T cells among tuberculosis patients: impact on prognosis and restoration of antigen specific IFN-γ producing T cells

• Published in: PloS one Vol. 7; no. 9; p. e44728
• Main Authors: Singh, Amar, Dey, Aparajita Ballave, Mohan, Anant, Sharma, Prabhat Kumar, Mitra, Dipendra Kumar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.09.2012; Public Library of Science (PLoS)
• Subjects: Adult; Antigens; Apoptosis; Biology; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell culture; Chronic illnesses; Cytokines; Cytometry; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Forkhead Transcription Factors - metabolism; Foxp3 protein; Gene expression; Human behavior; Humans; Immune response; Immune system; Immunology; Immunoregulation; Infectious diseases; Interferon; Interferon-gamma - metabolism; Interleukin 10; Interleukin 4; Interleukin-4 - metabolism; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Medicine; Middle Aged; Mycobacterium tuberculosis; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - metabolism; Restoration; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tropical diseases; Tuberculosis; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - pathology; Viral infections; Young Adult; γ-Interferon; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044728

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.