Circulating HLA-DR+CD4+ effector memory T cells resistant to CCR5 and PD-L1 mediated suppression compromise
Asma Ahmed1, Vasista Adiga1, Soumya Nayak1
1Laboratory of Immunology of HIV-TB co-infection, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India.
Plos Pathogens
|September 20, 2018
Summary
In pulmonary tuberculosis (PTB), regulatory T cells (Treg) struggle to suppress T effector cells (Teff). Activated Human Leukocyte Antigen (HLA)-DR+ Teff cells resist Treg suppression, driving inflammation in PTB patients.
Area of Science:
- Immunology
- Tuberculosis Research
- Cellular Immunology
Background:
- Chronic T cell activation is characteristic of pulmonary tuberculosis (PTB).
- Regulatory T cells (Treg) normally control T effector cells (Teff), but mechanisms in PTB are unclear.
- Teff cells in PTB patients are resistant to Treg suppression.
Purpose of the Study:
- To elucidate the mechanisms of T cell dysregulation in pulmonary tuberculosis.
- To identify the specific T cell subsets responsible for impaired Treg function in PTB.
- To investigate the molecular pathways mediating resistance to Treg suppression.
Main Methods:
- Analysis of circulating T cells from adults with PTB.
- Characterization of T effector (Teff) and regulatory T cell (Treg) subsets.
- Transcriptome analysis and antibody blocking experiments.
- Assessment of NFκB activation and cytokine expression.
Main Results:
- Teff cells from PTB patients resist Treg suppression due to an expansion of activated Human Leukocyte Antigen (HLA)-DR+ Teff cells.
- Depleting HLA-DR+ Teff cells restored sensitivity to Treg suppression.
- Resistance mechanisms involve increased expression of IFNG, IL17A, IL22, PD-L1, and β-chemokines.
- HLA-DR+ Teff cells resist Treg suppression via CCR5 and PD-L1 pathways, perturbing NFκB activation.
Conclusions:
- Activated HLA-DR+CD4+ T cells compromise Treg-mediated suppression in PTB.
- This impaired suppression contributes to disease-associated inflammation.
- Understanding these mechanisms offers novel insights into PTB pathogenesis.
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