M Wikén1, J Grunewald, A Eklund, J Wahlström. 1. Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. Maria.Wiken@ki.se
Abstract
OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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.
OBJECTIVES: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. DESIGN: 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. CONCLUSION: 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.
Authors: Caroline E Broos; Menno van Nimwegen; Henk C Hoogsteden; Rudi W Hendriks; Mirjam Kool; Bernt van den Blink Journal: Front Immunol Date: 2013-12-10 Impact factor: 7.561
Authors: Kerstin M Ahlgren; Tina Ruckdeschel; Anders Eklund; Jan Wahlström; Johan Grunewald Journal: BMC Pulm Med Date: 2014-03-22 Impact factor: 3.317