CD4 + CTLs in Fibrosing Mediastinitis Linked to Histoplasma capsulatum

Although fibrotic disorders are frequently assumed to be linked to T cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2/allergic disease spectrum. We have previously linked two human au...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2021-02, Vol.206 (3), p.524-530
Main Authors: Allard-Chamard, Hugues, Alsufyani, Faisal, Kaneko, Naoki, Xing, Kelly, Perugino, Cory, Mahajan, Vinay S, Wheat, Joseph L, Deepe, Jr, George S, Loyd, James, Pillai, Shiv
Format: Article
Language:English
Subjects:
Adult
CD4 Antigens - metabolism
Cells, Cultured
Cohort Studies
Female
Histoplasma - physiology
Histoplasmosis - immunology
Humans
Immunoglobulin G4-Related Disease - immunology
Lymphocyte Activation
Male
Mediastinitis - immunology
Middle Aged
Sclerosis - immunology
T-Lymphocytes, Cytotoxic - immunology
Th2 Cells - immunology
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Summary:Although fibrotic disorders are frequently assumed to be linked to T cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2/allergic disease spectrum. We have previously linked two human autoimmune fibrotic diseases, IgG4-related disease and systemic sclerosis, to the clonal expansion and lesional accumulation of CD4 CTLs. In both these diseases T cell accumulation was found to be sparse. Fibrosing mediastinitis linked to infection histologically resembles IgG4-related disease in terms of the inflammatory infiltrate and fibrosis, and it provides an example of a fibrotic disease of infectious origin in which the potentially profibrotic T cells may be induced and reactivated by fungal Ags. We show in this study that, in this human disease, CD4 CTLs accumulate in the blood, are clonally expanded, infiltrate into disease lesions, and can be reactivated in vitro by Ags. T cells are relatively sparse at lesional sites. These studies support a general role for CD4 CTLs in inflammatory fibrosis and suggest that fibrosing mediastinitis is an Ag-driven disease that may provide important mechanistic insights into the pathogenesis of idiopathic fibrotic diseases.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2000433