Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease
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-R...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2017.1280029 |
| _version_ | 1797684773974441984 |
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| author | Hamid Mattoo John H. Stone Shiv Pillai |
| author_facet | Hamid Mattoo John H. Stone Shiv Pillai |
| author_sort | Hamid Mattoo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:35:35Z |
| format | Article |
| id | doaj.art-f07bfe2a6f9543018efa79c8763f8f4b |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:35:35Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-f07bfe2a6f9543018efa79c8763f8f4b2023-09-15T10:01:06ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2017-01-01501192410.1080/08916934.2017.12800291280029Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related diseaseHamid Mattoo0John H. Stone1Shiv Pillai2Massachusetts General Hospital, Harvard Medical SchoolMassachusetts General Hospital, Harvard Medical SchoolMassachusetts General Hospital, Harvard Medical SchoolIgG4-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.http://dx.doi.org/10.1080/08916934.2017.1280029igg4-rdcd4+ ctlfibrosislymphoplasmacytic infiltrate |
| spellingShingle | Hamid Mattoo John H. Stone Shiv Pillai Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease Autoimmunity igg4-rd cd4+ ctl fibrosis lymphoplasmacytic infiltrate |
| title | Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease |
| title_full | Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease |
| title_fullStr | Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease |
| title_full_unstemmed | Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease |
| title_short | Clonally expanded cytotoxic CD4+ T cells and the pathogenesis of IgG4-related disease |
| title_sort | clonally expanded cytotoxic cd4 t cells and the pathogenesis of igg4 related disease |
| topic | igg4-rd cd4+ ctl fibrosis lymphoplasmacytic infiltrate |
| url | http://dx.doi.org/10.1080/08916934.2017.1280029 |
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