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Updated: Nov 25, 2025
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
CD4+CTLs in Fibrosing Mediastinitis Linked to Histoplasma capsulatum
Hugues Allard-Chamard1,2, Faisal Alsufyani1,3, Naoki Kaneko1,4
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139.
Abstract:
Although fibrotic disorders are frequently assumed to be linked to TH2 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 TH2 cell accumulation was found to be sparse. Fibrosing mediastinitis linked to Histoplasma capsulatum 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 H. capsulatum Ags. TH2 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.
Insights
Fibrotic disorders are often linked to TH2 cells, but this study finds CD4+CTLs drive fibrosis in infectious and autoimmune diseases. This suggests a broader role for CD4+CTLs in fibrotic conditions.
Area of Science:
- Immunology
- Pathology
- Fibrotic Disorders
Background:
- Fibrotic disorders are commonly, but not always, associated with TH2 cells.
- Previous research linked CD4+CTLs to autoimmune fibrotic diseases like IgG4-related disease and systemic sclerosis.
- TH2 cell accumulation is sparse in these autoimmune fibrotic conditions.
Purpose of the Study:
- To investigate the role of CD4+CTLs in fibrosing mediastinitis, an infectious fibrotic disease.
- To determine if CD4+CTLs are involved in fibrosing mediastinitis, similar to their role in autoimmune fibrotic diseases.
- To explore the potential of fibrosing mediastinitis as a model for understanding idiopathic fibrotic diseases.
Main Methods:
- Quantitative tissue analysis of inflammatory infiltrates.
- Blood and tissue sample collection from patients with fibrosing mediastinitis.
- In vitro assays to assess T cell reactivity to fungal antigens.
Main Results:
- CD4+CTLs accumulate in the blood and infiltrate lesions in fibrosing mediastinitis.
- Evidence of clonal expansion of CD4+CTLs in affected individuals.
- CD4+CTLs can be reactivated by fungal antigens (Histoplasma capsulatum) in vitro.
- TH2 cells are found to be sparse in fibrosing mediastinitis lesions.
Conclusions:
- CD4+CTLs play a significant role in fibrosing mediastinitis, an infectious fibrotic disease.
- Fibrosing mediastinitis is an antigen-driven disease, with CD4+CTLs responding to fungal antigens.
- These findings support a general role for CD4+CTLs in inflammatory fibrosis and offer insights into idiopathic fibrotic diseases.
