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Clonally expanded cytotoxic CD4 T cells and the pathogenesis of IgG4-related disease.
- Source :
-
Autoimmunity . Feb2017, Vol. 50 Issue 1, p19-24. 6p. - Publication Year :
- 2017
-
Abstract
- IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4+ T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated. Among the CD4+ T-cell subsets, Th2 cells were initially thought to contribute to IgG4-RD pathogenesis, but many previous studies were confounded by the concomitant history of allergic diseases in the patients studied and the failure to use multi-color staining to definitively identify T-cell subsets in tissue samples. More recently, using an unbiased approach to characterize CD4+ T-cell subsets in patients with IgG4-RD – based on their clonal expansion and ability to infiltrate affected tissue sites – CD4+ CTLs have been identified as the major CD4+ T-cell subset in disease lesions as well as in the circulation. CD4+ CTLs in affected tissues secrete pro-fibrotic cytokines including IL-1β, TGF-β1, and IFN-γ as well as cytolytic molecules such as perforin and granzymes A and B. In this review, we examine possible mechanisms by which activated B cells and plasmablasts may collaborate with the expanded CD4+ CTLs in driving the fibrotic pathology of the disease and describe the lacunae in the field and in our understanding of IgG4-RD pathogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08916934
- Volume :
- 50
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 121166657
- Full Text :
- https://doi.org/10.1080/08916934.2017.1280029