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MAIT cell counts are associated with the risk of hospitalization in COPD
Terezia Pincikova1,2,3,4, Tiphaine Parrot5, Lena Hjelte6,7
1Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden. terezia.pincikova@ki.se.
Background:
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with chronic inflammation in the airways. Mucosal-associated invariant T (MAIT) cells are unconventional, innate-like T cells highly abundant in mucosal tissues including the lung. We hypothesized that the characteristics of MAIT cells in circulation may be prospectively associated with COPD morbidity.
Methods:
COPD subjects (n = 61) from the Tools for Identifying Exacerbations (TIE) study were recruited when in stable condition. At study entry, forced expiratory volume in 1 s (FEV1) was measured and peripheral blood mononuclear cells were cryopreserved for later analysis by flow cytometry. Patients were followed for 3 years to record clinically meaningful outcomes.
Results:
Patients who required hospitalization at one or more occasions during the 3-year follow-up (n = 21) had lower MAIT cell counts in peripheral blood at study inclusion, compared with patients who did not get hospitalized (p = 0.036). In contrast, hospitalized and never hospitalized patients did not differ in CD8 or CD4 T cell counts (p = 0.482 and p = 0.221, respectively). Moreover, MAIT cells in hospitalized subjects showed a more activated phenotype with higher CD38 expression (p = 0.014), and there was a trend towards higher LAG-3 expression (p = 0.052). Conventional CD4 and CD8 T cells were similar between the groups. Next we performed multi-variable logistic regression analysis with hospitalizations as dependent variable, and FEV1, GOLD 2017 group, and quantity or activation of MAIT and conventional T cells as independent variables. MAIT cell count, CD38 expression on MAIT cells, and LAG-3 expression on both MAIT and CD8 T cells were all independently associated with the risk of hospitalization.
Conclusions:
These findings suggest that MAIT cells might reflect a novel, FEV1-independent immunological dimension in the complexity of COPD. The potential implication of MAIT cells in COPD pathogenesis and MAIT cells' prognostic potential deserve further investigation.
Insights
Lower counts and altered activation of mucosal-associated invariant T (MAIT) cells in COPD patients are linked to increased hospitalization risk. These findings suggest MAIT cells may offer a new way to predict COPD morbidity.
Area of Science:
- Immunology
- Pulmonology
Background:
- Chronic obstructive pulmonary disease (COPD) involves airway inflammation and airflow limitation.
- Mucosal-associated invariant T (MAIT) cells are innate-like T cells found in lung tissue.
Purpose of the Study:
- To investigate the prospective association between circulating MAIT cell characteristics and COPD morbidity.
- To determine if MAIT cell counts or activation states predict future hospitalizations in COPD patients.
Main Methods:
- Sixty-one stable COPD patients were recruited.
- Peripheral blood mononuclear cells were analyzed using flow cytometry.
- Patients were followed for 3 years to record hospitalizations.
Main Results:
- Lower MAIT cell counts and higher CD38 expression on MAIT cells were observed in patients hospitalized during follow-up.
- MAIT cell count, CD38 expression, and LAG-3 expression on MAIT and CD8 T cells were independently associated with hospitalization risk.
- Conventional CD4 and CD8 T cell counts did not differ between hospitalized and non-hospitalized groups.
Conclusions:
- MAIT cells may represent a novel, FEV1-independent immunological marker in COPD.
- Further research is warranted to explore the role of MAIT cells in COPD pathogenesis and their prognostic potential.
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