Frequency and phenotypical alterations of unconventional T cells in cystic fibrosis

Introduction: Cystic fibrosis (CF) is characterized by a sustained and persistent inflammation within the lungs. Unconventional T lymphocytes, a heterogeneous class of T lymphocytes (e.g. MAIT, γδT, and iNKT cells) play a key role in orchestrating the inflammatory response at mucosal sites and participate in the fine-tuning of the host inflammatory response. Aims and objectives: To evaluate the frequency and state of activation of unconventional T lymphocytes in adult patients with CF. We hypothesized that unconventional T cell response could be dysregulated and contribute to the chronic inflammation observed in CF. Methods: We conducted a prospective study by enrolling 62 patients from the Cystic Fibrosis Center of Tours, France, between April 2019 and October 2020. MAIT, γδT, and iNKT cells were measured in patient’s blood as compared to 49 healthy controls. Activation status was assessed by monitoring CD-69 and PD-1 markers by flow cytometry. Results: In comparison to healthy controls, γδT cells were significantly increased in the peripheral blood of CF patients (9.2 % vs 3.6 % of T-lymphocytes, p < 0.001), whereas MAIT and iNKT proportions were decreased (respectively 1.4 % vs 2.6%, p < 0.01 and 0.04 % vs 0.1 %, p< 0.001). All unconventional T cell subsets displayed an activated phenotype in patients with CF compared to healthy controls. Conclusion: The relative proportion of all circulating unconventional T cell subsets differs significantly in CF patients as compared to healthy controls. In addition, these subsets display a highly activated phenotype. Altogether, this supports the hypothesis that unconventional T cells play a role in the regulation of the inflammatory response during CF.