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

Objective:   Sarcoidosis is an inflammatory disorder in which elevated numbers of activated T cells are found in the lung. HLA-DRB1*0301(pos) (DR3(pos) ) patients are characterized by good prognosis and an accumulation of lung CD4(pos) 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.

Methods:   Bronchoalveolar lavage (BAL) fluid and whole blood were obtained from a total of 22 patients with sarcoidosis, of whom 11 were DR3(pos) . 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:   DR3(pos) patients had fewer FOXP3(pos) (regulatory) CD45RO(pos) (memory) BAL T cells than DR3(neg) patients. Fewer AV2S3(pos) T cells were FOXP3(pos) , compared with AV2S3(neg) cells, thus indicating an effector function and not a regulatory role for this subset. Fewer lung and blood AV2S3(pos) T cells were CD25(pos)  CD27(pos) , and more were CD25(neg)  CD27(neg) and CD69(pos) , compared with AV2S3(neg) T cells, indicating a higher degree of differentiation and activation in both compartments.

Conclusions:   Our main findings were a lower proportion of regulatory T cells in DR3(pos) patients, together with the accumulation of AV2S3(pos) 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 DR3(pos) patients and could thus help to explain the spontaneous recovery typically seen in these patients.