T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.

Grünewald, Johan; Olerup, Olle; Persson, Ulla; Öhrn, Mary; Wigzell, Hans; Eklúnd, Anders

doi:10.1073/pnas.91.11.4965

Cited by 117 publications

(107 citation statements)

References 21 publications

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“…In our evaluation of 8 sarcoidosis patients, 4 of whom were positive for DRB1*03, we did not detect any CD4ϩ BV3ϩ expansion (31). We also did not find expansions of CD4ϩ BV3ϩ cells in BAL fluid samples from patients with allergic asthma either before or after allergen challenge (3 of 8 patients studied were DRB1*03 positive) (21).…”

Section: Discussionmentioning

confidence: 46%

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

Englund¹,

Wahlström²,

Fathi³

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate T cell receptor (TCR) expression in 3 different compartments that could be involved in patients with myositis: muscle, lung, and peripheral blood.Methods. Nine patients with polymyositis (PM), dermatomyositis, or inclusion body myositis underwent bronchoscopy and bronchoalveolar lavage (BAL) as well as muscle biopsy and blood sampling. A panel of 19 monoclonal antibodies specific for TCR V ␤ (BV) and V ␣ (AV) were used to characterize the TCR profile in CD4؉ and CD8؉ T cell populations in BAL fluid and peripheral blood by flow cytometry. Muscle biopsy tissues were analyzed by immunohistochemistry. Patients were also typed for HLA-DRB1 and DRB3 alleles.Results. A total of 17 T cell expansions were detected in BAL fluid, 6 in the CD4؉ T cell population and 11 in the CD8؉ T cell population. Four T cell expansions were detected in peripheral blood. A selective TCR V usage was found in muscle. Two PM patients, both of whom had BAL fluid BV3؉ T cell expansions in the CD4 population and in whom BV3 was also a prominent TCR V segment in muscle tissue, shared the HLA-DRB1*03 allele. These 2 patients were the only ones who were positive for anti-Jo-1 antibody.Conclusion. We found a restricted accumulation of T lymphocytes expressing selected TCR V-gene segments in the target organ compartments (i.e., lung and muscle). The occurrence of shared TCR gene segment usage in muscle and lungs could suggest common target antigens in these organs.

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Section: Discussionmentioning

confidence: 46%

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

Englund¹,

Wahlström²,

Fathi³

et al. 2007

Arthritis & Rheumatism

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“…Together with HLA and T-cell receptor (TCR) genes, Gm and km allotypes account for the most informative triad of genes involved in immune-related diseases, but so far have not been extensively studied in sarcoidosis. GRUNEWALD et al [12] reported a positive association between the TCR variable region a2.3+, in CD4+ lung T-cells and the HLA-DR3(17),DQ2 haplotype in sarcoidosis.…”

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confidence: 99%

HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic structure

Martinetti

Tinelli

et al. 2000

Eur Respir J

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The aetiology of sarcoidosis is still unknown. Environmental exposures are believed to interact with genetic factors in determining the pattern of sarcoidosis presentation, progression and prognosis. The frequency of serological polymorphism of immunoglobulin G heavy chain (Gm) and κ light chain (κm) markers in 107 patients with biopsy‐proven sarcoidosis and in 227 controls, and their interactions with histocompatibility leukocyte antigen (HLA) class I, II, and III markers, were studied. A “protective” effect of the Gm(3 5*) phenotype in the sarcoid group versus controls (p‐value for number of specificities tested (pc)=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients with advanced chest radiographic stage (Chi‐squared (two degrees of freedom)(χ2(2df) 17.61, pc=0.0058) were observed. With reference to epistatic interactions, the combination Gm(3 23 5*)/BfS had a “protective” effect towards stage II (χ2(2df) 13.86, pc=0.043). Finally, correspondence analysis defined two clusters: HLA‐DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with stage II, and HLA‐DR3, C4AQ0, κm(1) and Gm(3 23 5*) associated with stage I. These data further support the hypothesis that sarcoidosis results from an interplay of environmental factors and genes, each contributing to the susceptibility/resistance to and/or the clinical heterogeneity of the disease. In addition, these data provide the first evidence of an interaction between immunoglobulin G heavy chain/κ light chain markers and histocompatibility leukocyte antigen class III genes in a disease.

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Section: Discussionmentioning

confidence: 95%

“…AV2S3z CD4z T-cells accumulating in the lungs, was previously identified only in HLA-DR17 positive Scandinavian Caucasian sarcoidosis patients [20,22]. In fact, the association between lung accumulated CD4z AV2S3z T-lymphocytes and HLA-DR17 in Scandinavian patients with pulmonary sarcoidosis is extremely strict, provided there is an active disease [20,22]. Moreover, BAL AV2S3z T-cells were recently found to correlate with clinical features of the disease [23] and to express a panel of activation markers indicative of select stimulation of this particular subset [24].…”

Section: Discussionmentioning

confidence: 99%

“…A bronchoscopy was performed and transbronchial biopsies showed occurrence of nonnecrotizing epithelioid cell granulomas, thus supporting the diagnosis. Bronchoalveolar lavage (BAL) was also performed [20] and an increased concentration of BAL cells was found (663.2610 6 ?L -1 ; normal range in the laboratory 50 -150610 6 ?L -1 ). The BAL differential count showed a slight decrease of alveolar macrophages (81%) and an increase of lymphocytes (18.8%).…”

Section: Case Reportmentioning

confidence: 99%

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Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis

Grünewald

Eklúnd

2001

Eur Respir J

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Presented is a sarcoidosis patient of African origin, who was adopted at an early age and grew up in Sweden.This patient displayed an immune response identical to that previously reported in human leukocyte antigen (HLA)-DR17 positive Caucasian sarcoidosis patients in Scandinavia, with T-cell receptor AV2S3+ T-cells accumulating in the lungs. HLA typing also established that she was DR17 positive, which is a rare HLA type for individuals of African origin.To the authors' knowledge, this specific immune response has not previously been reported in patients of African origin. Moreover, the clinical manifestations of sarcoidosis were similar to those known to be strongly linked to HLA-DR17 in Scandinavians,i.e.with Löfgren's syndrome.The case presented here suggests certain human leukocyte antigen genes to be strongly linked to specific immune responses that are identical irrespective of the racial background. If such an immune response were important for the subsequent clinical manifestations, this case would argue for the importance of human leukocyte antigen genes in the genetic predisposition to sarcoidosis.

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T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients.

Cited by 117 publications

References 21 publications

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

Restricted T cell receptor BV gene usage in the lungs and muscles of patients with idiopathic inflammatory myopathies

HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic structure

Human leukocyte antigen genes may outweigh racial background when generating a specific immune response in sarcoidosis

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