Background/Purpose:

CD4⁺CD25^lowGITR⁺ T lymphocytes expressing FoxP3 and showing regulatory function have been recently described in healthy donors (HD). The objective of this study was to determine whether CD4⁺CD25^lowGITR⁺ T lymphocytes are detected in peripheral blood (PB) and broncho-alveolar lavage (BAL), to investigate their in patients with interstitial lung disease (ILD) secondary to primary Sjogren’s syndrome (pSS).

Methods:

CD4⁺CD25^lowGITR⁺ cells circulating in PB and BAL of patients with pSS-ILD were isolated by MACS technique, and their phenotype was studied by flow cytometry and real-time PCR, and their function was studied by in vitro co-culture. CD4⁺CD25^lowGITR⁺ cells infiltrating salivary glands (SGs) were revealed by immunohistochemistry.

Results: Nineteen patients with idiopathic pulmonary fibrosis (IPF) and 13 patents with pSS-ILD were enrolled in the study. Ten healthy donors were concluded in the study, too. Results indicated that conventional CD4⁺CD25^high regulatory T cells (Tregs) are decreased, whereas CD4⁺CD25^lowGITR⁺ cells are expanded in the PB of pSS-ILD as compared with HD and IPF. Phenotypic analysis demonstrated that CD4⁺CD25^lowGITR⁺ cells display Treg markers, including FoxP3, TGF-β and IL-10, and functional experiments demonstrated that they exert a strong inhibitory activity against autologous effector cells. The number of CD4⁺CD25^lowGITR⁺ cells infiltrating in the SG were positively correlated with the inflammatory infiltrating of CD4⁺CD25^lowGITR⁺ cells in BAL.

Conclusion:

The present data demonstrate that CD4⁺CD25^lowGITR⁺ cells are detectable in PB and BAL of pSS-ILD patients. These cells, displaying Treg phenotype and function, are present in SG inflamed tissues and are in accordance with that infiltrating in BAL.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/detection-of-cd4cd25lowgitr-t-lymphocytes-in-sjogrens-syndrome-interstitial-lung-disease/