You are here: Home Published Research T regulatory cells and PD-1+ T cells contribute to effector T cell dysfunction in COPD patients.

Suresh G Kalathil, Amit A Lugade, Vandana Pradhan, Austin Miller, Ganapathi I Parameswaran, Sanjay Sethi, and Yasmin Thanavala (2014)

T regulatory cells and PD-1+ T cells contribute to effector T cell dysfunction in COPD patients.

American journal of respiratory and critical care medicine.

Rationale: Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from COPD patients prone to exacerbations with non-typeable Haemophilus influenzae (NTHI) have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective anti-bacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC) and exhausted T effector cells (PD-1+) in COPD patients, as these cells are known to play a pivotal role in suppressing immune responses. Objectives: We performed an in-depth characterization of Tregs, T effector cells and MDSC in COPD and correlated their levels and function with disease severity. Methods: Treg, effector T cell, and MDSC frequency from COPD patients and healthy subjects PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured by in vitro suppression assay. The frequency of interferon-γ producing T cells and T cell proliferation were measured after blocking CTLA-4 and PD-1. Plasma pro-inflammatory and immunosuppressive cytokine levels were measured. Measurements and Main results: Significantly increased levels of Tregs, MDSC and PD-1+ exhausted effector T cells were present in COPD patients compared to healthy subjects. Tregs from COPD patients suppressed P6-specific T cell proliferation to a greater extent than Tregs from healthy subjects. Plasma levels of Treg-generated cytokines, IL-10 and TGF-β were elevated. Blockade of CTLA-4 resulted in significant augmentation of T cell IFN-γ production in COPD patients. Conclusion: Functionally suppressive Tregs, MDSCs and exhausted PD-1+ T cells contribute to effector T cell dysfunction in COPD.

 
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