Sara Iranparast; Farhad Seif; Sanaz Tayebi; Farhad Abolnezhadian; Moosa Sharifat; Alireza Fazaeli; Neda Roshanravan; Azam Samei; Sholeh Khajoei
Abstract
Follicular helper T (TFH) cells are a subset of effector CD4+ T cells that support the differentiation of antigen-specific B cells in the germinal center. TFH cells are distinct from other established CD4+ T cell subsets and possess a list of transcription factors, including BCL6, IRF4, c-Maf, Batf, ...
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Follicular helper T (TFH) cells are a subset of effector CD4+ T cells that support the differentiation of antigen-specific B cells in the germinal center. TFH cells are distinct from other established CD4+ T cell subsets and possess a list of transcription factors, including BCL6, IRF4, c-Maf, Batf, NFAT1-2, and STAT3. The mentioned factors direct several activities such as cell differentiation, migration to the follicles, cell-to-cell interaction, as well as cell programming. Given that TFH cells are essential for the germinal center formation, affinity maturation and the development of most high-affinity antibodies. TFH cells may play crucial roles in different pathologic conditions, particularly autoimmune diseases. However, the mechanisms that cause functional differences of TFH cell responses are not exactly defined. In this review first the immunological profile of TFH cells will be discussed then attempts will be made to give a broad picture on the role of this key subset of T cells in autoimmune diseases.
Fatemeh Zaremehrjardi; Leila Baniadam; Farhad Seif; Saba Arshi; Mohamad Hasan Bemanian; Sima Shokri; Afshin Rezaeifar; Morteza Fallahpour; Mohammad Nabavi
Abstract
Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting for the primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated and regulatory T-cells, which can bind to CD80/CD86 molecules on ...
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Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting for the primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated and regulatory T-cells, which can bind to CD80/CD86 molecules on antigen-presenting cells as a negative regulator. Here, we describe a 24-year-old male born from consanguineous parents with heterozygous CTLA-4 mutation who presented with multiple autoimmune diseases. His past clinical history revealed alopecia areata atfour years old and subsequently, he developed Evans syndrome, type 1 diabetes mellitus, hypothyroidism, and chronic diarrhea while chronic rhinosinusitis and cytomegalovirus (CMV) colitis were the only infectious manifestations. Immunologic investigations revealed: low B cell count, abnormal Lymphocyte transformation test (LTT) to phytohemagglutinin (PHA), and hypogammaglobulinemia. Although all available treatments such as Intravenous Immunoglobulin (IVIG) therapy, immunosuppressive drugs, and antibiotic therapy were applied, diarrhea was not controlled due to colitis, which remained challenging. Whole exome sequencing was performed and the result showed heterozygous variant CHR2.204,735,635 G>A in the CTLA-4 gene, which was confirmed by the Sanger method. CTLA4 haploinsufficiency leads to autoimmune disorders, recurrent respiratory infections, hypogammaglobulinemia, lymphoproliferation with organ infiltration, and lymphocytic interstitial lung disease.
