15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Histopathology of Labial Salivary Glands in Primary Sjögren's Syndrome: Focusing on Follicular Helper T Cells in the Inflammatory Infiltrates

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recently, we revealed the importance of follicular helper T cells (T FH) in the pathogenesis of primary Sjögren's syndrome (pSS). In the present study, we focused on the site of the inflammation and determined the composition of lymphocyte infiltration in labial salivary gland (LSG) biopsies with special emphasis on T FH and germinal center B cells. We selected tissue blocks obtained from ten patients at the time of disease onset. Detection of cell specific markers was performed with immunohistochemical and immunofluorescence stainings. We evaluated patients' clinical and laboratory features retrospectively and assessed the relation between disease course and early histopathological findings. LSG biopsies were graded based on the extension and arrangement level of periductal inflammatory cell infiltrates. T FH cell markers (CD84, PD-1, and Bcl-6) occurred predominantly in more organized structures with higher focus scores. The coexpression of CD3 and Bcl-6 markers clearly identified T FH cells close to Bcl-6 + B cells with the typical formation of germinal centers. Systemic features were developed later in the disease course only in patients with highly structured infiltrates and the presence of T FH cells. Our observations suggest that the presence of T FH cells in LSGs at the disease onset may predict a more pronounced clinical course of pSS.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells

          Memory B and plasma cells (PCs) are generated in the germinal center (GC). As PD-1 is highly expressed in T follicular helper cells (TFH), we investigated the role of PD-1 signaling in the humoral response. We found that PD-L1 and PD-L2 are upregulated on GC B cells. Pdcd1lg2 −/− , CD274 −/− Pdcd1lg2 −/− and Pdcd1 −/− mice had reduced numbers of long-lived PCs. The mechanism involved increased GC cell death and decreased TFH cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had higher affinity. PD-1 expression on T cells and PD-L2 expression on B cells controlled TFH and PC numbers. Thus, PD-1 regulates selection and survival in the GC, impacting the quantity and quality of long-lived PCs.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The origins, function, and regulation of T follicular helper cells

            The generation of high-affinity antibodies (Abs) plays a critical role in the neutralization and clearance of pathogens and subsequent host survival after natural infection with a variety of microorganisms. Most currently available vaccines rely on the induction of long-lived protective humoral immune responses by memory B cells and plasma cells, underscoring the importance of Abs in host protection. Ab responses against most antigens (Ags) require interactions between B cells and CD4+ T helper cells, and it is now well recognized that T follicular helper cells (Tfh) specialize in providing cognate help to B cells and are fundamentally required for the generation of T cell–dependent B cell responses. Perturbations in the development and/or function of Tfh cells can manifest as immunopathologies, such as immunodeficiency, autoimmunity, and malignancy. Unraveling the cellular and molecular requirements underlying Tfh cell formation and maintenance will help to identify molecules that could be targeted for the treatment of immunological diseases that are characterized by insufficient or excessive Ab responses.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Germinal centres: role in B-cell physiology and malignancy.

              Over the past several years, studies on normal and malignant B cells have provided new insights into the unique physiology of the germinal centre (GC). In particular, advances in technology have allowed a more precise dissection of the phenotypes of GC B cells and the specific transcriptional programmes that are responsible for this phenotype. Furthermore, substantial progress has been made in the understanding of the mechanism controlling the exit of B cells from the GC and the decision to become a memory B cell or plasma cell. This Review focuses on these recent advances and discusses their implications for the pathogenesis of B-cell lymphomas.
                Bookmark

                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2014
                7 August 2014
                : 2014
                : 631787
                Affiliations
                1Division of Clinical Immunology, Medical Center, University of Debrecen, Moricz Zs. Street 22, Debrecen 4032, Hungary
                2Department of Pathology, Medical Center, University of Debrecen, Nagyerdei Boulevard 98, Debrecen 4032, Hungary
                Author notes

                Academic Editor: Peter Szodoray

                Author information
                http://orcid.org/0000-0002-0079-3659
                http://orcid.org/0000-0002-4698-3351
                Article
                10.1155/2014/631787
                4142299
                25177110
                4d4ff6d7-0d80-4677-82e0-5ffee0f53b86
                Copyright © 2014 Krisztina Szabo et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 May 2014
                : 11 July 2014
                : 11 July 2014
                Categories
                Research Article

                Immunology
                Immunology

                Comments

                Comment on this article