Multiparameter phenotyping of T-cell subsets in distinct subgroups of patients with pulmonary sarcoidosis


Maria Wikén, Department of Medicine Solna, Respiratory Medicine Unit, Lung Research Laboratory L4:01, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden.
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Abstract.  Wikén M, Grunewald J, Eklund A, Wahlström J (Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden). Multiparameter phenotyping of T-cell subsets in distinct subgroups of patients with pulmonary sarcoidosis. J Intern Med 2012; 271: 90–103.

Objectives.  Sarcoidosis is an inflammatory disorder in which elevated numbers of activated T cells are found in the lung. HLA-DRB1*0301pos (DR3pos) patients are characterized by good prognosis and an accumulation of lung CD4pos T cells expressing the T-cell receptor (TCR) gene segment AV2S3. Our aim was to phenotype lung and blood T-cell subsets in distinct patient groups to better understand the function of these subsets.

Design.  Bronchoalveolar lavage (BAL) fluid and whole blood were obtained from a total of 22 patients with sarcoidosis, of whom 11 were DR3pos. Using eight-colour flow cytometry, phenotyping of T cells was performed with regard to CD3, CD4, CD8, CD25, CD27, CD45RO, CD57, CD69, CD103, FOXP3 and TCR AV2S3.

Results.  DR3pos patients had fewer FOXP3pos (regulatory) CD45ROpos (memory) BAL T cells than DR3neg patients. Fewer AV2S3pos T cells were FOXP3pos, compared with AV2S3neg cells, thus indicating an effector function and not a regulatory role for this subset. Fewer lung and blood AV2S3pos T cells were CD25pos CD27pos, and more were CD25neg CD27neg and CD69pos, compared with AV2S3neg T cells, indicating a higher degree of differentiation and activation in both compartments.

Conclusion.  Our main findings were a lower proportion of regulatory T cells in DR3pos patients, together with the accumulation of AV2S3pos T cells with a highly activated effector phenotype in the lungs of these patients. This may provide for efficient elimination of a harmful antigen in DR3pos patients and could thus help to explain the spontaneous recovery typically seen in these patients.