Expression of Th1 markers by lung accumulated T cells in pulmonary sarcoidosis.
OBJECTIVE
The balance between Th1 and Th2 T cells, classified by virtue of their cytokine production can in an immune response influence the phenotype and progression of several clinical diseases. In this study, we examined the expression of Th1 associated chemokine and cytokine receptors CXCR3, CCR5, and interleukin (IL)-12R, IL-18R, respectively, as well as of the Th2 associated chemokine receptors CCR4 and CXCR4 on CD4+ and CD8+ T cells.


METHODS
Eighteen patients with untreated pulmonary sarcoidosis.


METHODS
We used monoclonal antibodies and flow cytometry to analyse the expression of chemokine receptors CXCR3, CXCR4, CCR4 CCR5 and cytokine receptors IL-12R, IL-18R in combination with anti-CD4 and anti-CD8 mAbs in bronchoalveolar lavage fluid (BAL) and peripheral blood lymphocytes (PBL) from sarcoidosis patients.


RESULTS
There were significantly more BAL CD4+ T cells expressing CXCR3, CCR5, IL-12R and IL-18R compared with paired PBL CD4+ T cells. In contrast, the Th2 associated chemokine receptors CXCR4 and CCR4 were expressed by a fewer percentage of BAL CD4+ compared with PBL CD4+ T cells. There was a positive correlation between the percentage of BAL lymphocytes and the number of CXCR3 and CCR5 expressing CD4+ BAL T cells. Also, the number of CD4+ IL-18R+ BAL fluid cells correlated negatively with disease duration.


CONCLUSIONS
The lung accumulation of CXCR3, CCR5, IL-12R and IL-18R expressing T cells is in line with previous reports showing elevated levels in the lung of the corresponding ligands in sarcodosis. Blocking such ligands and/or receptors may develop into a future immunomodulatory therapy.
Katchar
K
K
Department of Medicine, Division of Respiratory Medicine, Karolinska Hospital, Stockholm, Sweden. kia.katchar@ks.se
Eklund
A
A
Grunewald
J
J
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D053727:Interleukin-18 Receptor alpha Subunit; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18