Antigen-specific multifunctional T-cells in sarcoidosis patients with Löfgren’s syndrome

Wikén, Maria; Ostadkarampour, Mahyar; Eklúnd, Anders; Willett, Matthew; Chen, Edward; Möller, David R.; Grünewald, Johan; Wahlström, Jan

doi:10.1183/09031936.00166110

Cited by 18 publications

(20 citation statements)

References 39 publications

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“…Another bioinformatic study predicted that sarcoidosis patients express HLA-DR alleles that recognize mycobacterial epitopes with higher affinity than HLA-DR sequences found in control patients with tuberculosis infection, suggesting that sarcoidosis may represent an antigendriven hypersensitivity to trace amounts of mycobacterial antigens [106]. A study from Sweden found that recombinant mKatG induced a pronounced multifunctional Th1 effector response with simultaneous IFNγ and TNF release in T cells expressing the AV2S3 T-cell receptors suggesting such enhanced Th1 responses may contribute to the self-remitting Löfgren syndrome in Scandinavian patients, many of whom express HLA-DRB1*0301 alleles (Table 1) [107].…”

Section: Role Of Mycobacterial Organisms In Sarcoidosismentioning

confidence: 98%

Etiologies of Sarcoidosis

Chen

Möller

2015

Clinic Rev Allerg Immunol

125

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Since sarcoidosis was first described more than a century ago, the etiologic determinants causing this disease remain uncertain. Studies suggest that genetic, host immunologic, and environmental factors interact together to cause sarcoidosis. Immunologic characteristics of sarcoidosis include non-caseating granulomas, enhanced local expression of T helper-1 (and often Th17) cytokines and chemokines, dysfunctional regulatory T-cell responses, dysregulated Toll-like receptor signaling, and oligoclonal expansion of CD4+ T cells consistent with chronic antigenic stimulation. Multiple environmental agents have been suggested to cause sarcoidosis. Studies from several groups implicate mycobacterial or propionibacterial organisms in the etiology of sarcoidosis based on tissue analyses and immunologic responses in sarcoidosis patients. Despite these studies, there is no consensus on the nature of a microbial pathogenesis of sarcoidosis. Some groups postulate sarcoidosis is caused by an active viable replicating infection while other groups contend there is no clinical, pathologic, or microbiologic evidence for such a pathogenic mechanism. The authors posit a novel hypothesis that proposes that sarcoidosis is triggered by a hyperimmune Th1 response to pathogenic microbial and tissue antigens associated with the aberrant aggregation of serum amyloid A within granulomas, which promotes progressive chronic granulomatous inflammation in the absence of ongoing infection.

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Section: Role Of Mycobacterial Organisms In Sarcoidosismentioning

confidence: 98%

Etiologies of Sarcoidosis

Chen

Möller

2015

Clinic Rev Allerg Immunol

125

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“…1 CD4 1 T cells have been classified as effector cells, as they possess negligible FoxP3 expression [9] and also produce proinflammatory cytokines such as IFN-g and TNF-a when stimulated in vitro [45]. Intriguingly, despite their well-documented T effector cell phenotype, the expression of ICOS on BAL AV2S3…”

Section: Cells) and Non-regulatory T Cells (Cd4mentioning

confidence: 99%

Pulmonary sarcoidosis is associated with high-level inducible co-stimulator (ICOS) expression on lung regulatory T cells – possible implications for the ICOS/ICOS-ligand axis in disease course and resolution

Sakthivel

Grünewald

Eklúnd

et al. 2015

Clinical and Experimental Immunology

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SummarySarcoidosis is a granulomatous inflammatory disorder of unknown aetiology. The increased frequency of activated lung CD41 T cells with a T helper type 1 (Th1) cytokine profile in sarcoidosis patients is accompanied by a reduced proportion and/or impaired function of regulatory T cells (T regs ). Here we evaluated the expression of the inducible co-stimulator (ICOS) on lung and blood CD4 1 T cell subsets in sarcoidosis patients with different prognosis, by flow cytometry. Samples from the deep airways were obtained by bronchoalveolar lavage (BAL). We show that T regs from the inflamed lung of sarcoidosis patients were characterized by a unique ICOS high phenotype. High-level ICOS expression was restricted to T regs from the inflamed lung and was absent in blood T regs of sarcoidosis patients as well as in lung and blood T regs of healthy volunteers. In addition, lung T regs exhibited increased ICOS expression compared to sarcoid-specific lung effector T cells. Strikingly, ICOS expression on T regs was in particularly high in the lungs of L€ ofgren's syndrome (LS) patients who present with acute disease which often resolves spontaneously. Moreover, blood monocytes from LS patients revealed increased ICOS-L levels compared to healthy donors. Sarcoidosis was associated with a shift towards a nonclassical monocyte phenotype and the ICOS-L high phenotype was restricted to this particular monocyte subset. We propose a potential implication of the ICOS/ICOS-L immune-regulatory axis in disease activity and resolution and suggest to evaluate further the suitability of ICOS as biomarker for the prognosis of sarcoidosis.

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“…The authors found in an earlier work that mKatG stimulation of T-cells from patients with Löfgren syndrome react with a strong simultaneous release of TNF and interferon (IFN)-γ, whereas non-Löfgren patients' T-cells responded only with the release of IFN-γ [19]. Once more, TCR Vα2.3 T-cells react more strongly to the antigen than T-cells bearing other TCR subfamilies.…”

mentioning

confidence: 93%