title: T helper type 2 differentiation is associated with induction of antibacterial defense mechanisms in blood lymphocytes of patients with sarcoidosis.
abstract: Whereas sarcoidosis is characterized by an excessive inflammatory immune response mainly at the pulmonary site, circulating T lymphocytes poorly respond to antigen challenge. It has been suggested, that the extensive local inflammation might be triggered by bacterial pathogens. Recently, it has been shown that this paradoxically immunological situation likely results from a disequilibrium between effector and regulatory T lymphocytes (T(reg)). Here, we apply a DNA microarray approach in order to analyze circulating T cells for specific dysregulatory events, which should provide detailed insights in the impairment of cell-mediated immunity. Gene expression profiles were performed from peripheral blood T lymphocytes of untreated patients with pulmonary sarcoidosis (stage I) (n = 3) and a control group consisting of healthy donors (n = 3). Circulating T lymphocytes in sarcoidosis exhibit a specific gene expression pattern of molecules that are primarily involved in immune responses and lymphocyte signalling. Compared to controls patients with sarcoidosis display also alterations in gene expression of molecules with bacteriolytic and chemotactic function. Among others, array analysis resulted in increased transcript levels of Th2 immune response, whereas genes coding for molecules involved in Th1 differentiation are down-regulated. Furthermore, genes encoding proteins representing primordial antimicrobial peptides which may mobilise immunocompetent T cells and other inflammatory cells are up-regulated. This observation supports recent reports suggesting that bacterial antigens play a role in the pathogenesis of sarcoidosis. However, the results of our study indicate an unbalanced immune response towards Th2 in the peripheral blood of patients with sarcoidosis.
authors.affiliation: Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany.
authors.forename: Sya N
authors.initials: SN
authors.lastname: Ukena
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuehner
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017565:Sarcoidosis, Pulmonary / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D014157:Transcription Factors