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Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
Two tyrosine kinases—Lck (Lymphocyte-specific protein tyrosine kinase) and ZAP70 (zeta-associated protein 70) play a critical role in the selection of CD4 and CD8 T cells, respectively. Patients with congenital deficiency of Lck have severe combined immunodeficiency because of the failure of CD4 differentiation; ZAP70 deficiency results in a severe defect of CD8 T cell differentiation. A small fraction of T cells, mostly of gd subtype, is negative for both CD4 and CD8 (double negative) (Carding et al. 2002).
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
The productively rearranged β chain will be present in the cytoplasm for several days prior to TCRα gene rearrangement. During that period, the β chain will associate with a protective polypeptide, known as the pre-Tα. When the β chain/pre-Tα associates with CD3 molecules and is transported to the cell membrane, the pre-TCR is formed. CD3 is a complex of five unique subunits designated γ, δ, ε, ζ, and η (note that the γ and δ chains of the CD3 unit are distinct from the γδ chains of the TCR1). The CD3γδε trimolecular complex is synthesized first and remains intracytoplasmic, where it becomes associated with pre-Tα molecules. Soon thereafter, the CD3ζ chains are synthesized and become associated to the CD3 complex. Once the ζ chain has been added to the CD3 molecule, the whole CD3-pre-Tα complex is transported from the Golgi apparatus to the cell membrane. A critical characteristic of the ζ chain is its long intracytoplasmic tail, which has affinity for the ζ-associated protein kinase (ZAP70). The association of ZAP70 to the ζ chain is critical for further differentiation of the T cell. The congenital absence of ZAP70 is associated with a block at the DN stage of T cell development.
Immunology of Aging and Cancer Development
Published in Shamim I. Ahmad, Aging: Exploring a Complex Phenomenon, 2017
T. Fulop, J. M. Witkowski, G. Dupuis, A. Le Page, A. Larbi, G. Pawelec
The formation of the immune synapse between the APC and T cell is altered as the membrane of old T cells becomes more rigid, resulting in decreased lipid raft coalescence, which is indispensable for the correct functioning of the immune synapse [93]. This contributes to a decreased signaling in T cells by impairing activation of the essential tyrosine kinase, Lck [94–96] due to decreased activation of ZAP70. The primary mechanism responsible for decreased Lck activation is the inability to modulate phosphatase inhibitory activity [96]. In vitro repression of the SHP-1 phosphatase can restore the proliferation and IL-2 secretion of T cells in the aged [96], as was also demonstrated for several other phosphatases of the DUSP family [97,98].
Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients
Published in Hematology, 2022
Yikai Zhang, Xiangbo Zeng, Xianfeng Zha, Jing Lai, Guangxiao Tan, Shaohua Chen, Xibao Yu, Yangqiu Li, Ling Xu
T cell immunity is an important component for maintaining anti-tumor and antivirus capability in the body; however, T cell immune deficiency is common in patients with tumors and viral infections. In recent years, anti-programmed death receptor (PD-1) [8] and chimeric antigen receptor T (CAR-T) cell [9–15] have significantly improved clinical outcome for lymphoma and leukemia patients in clinical trials. T cell immunotherapy has become an important method for tumor treatment. Our team and others have found that T cell dysfunction is a common characteristic of CML patients and that it is closely related to disease status, prognosis, and TKI treatment effects [6,16–19]. Based on abnormalities in molecules related to the T cell receptor (TCR) signaling pathway in T cells, such as CD3ζ and ZAP70, regulation of these molecules could only partially restore T cell function [20–23]. Thus, further investigation of the mechanism underlying T cell dysfunction is needed to determine the regulatory approach and to enhance T cells against leukemia.
Platelets after burn injury – hemostasis and beyond
Published in Platelets, 2022
B. Z. Johnson, A. W. Stevenson, L. W. Barrett, M. W Fear, F. M. Wood, M. D. Linden
CD4 + T-regulatory cells (Tregs) play a crucial role in controlling inflammatory responses, limiting the extent of tissue damage. A mouse model of 25% TBSA (severe) injury with or without depletion of Tregs or platelets has been used to investigate in vivo platelet–Treg interactions [100]. The authors noted a “biologically significant” increase in zeta-chain-associated protein kinase 70 (ZAP-70) and protein kinase C-theta (PKC-θ) in lymph node Tregs 2 h following burn injury, which was decreased in the platelet-depleted model. Increased activation was not seen in splenic Tregs, however in the platelet-depleted model ZAP-70 and PKC-θ expression was again lower. ZAP-70 is necessary for T-cell receptor (TCR) signaling, and therefore required for functional T-cell responses. Conversely, evidence suggests PKC-θ is dispensable for Treg function, and potentially negatively regulates suppressive capacity; however, it seems to play a role in Treg differentiation and development [101].
Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR)
Published in Immunological Investigations, 2021
Farzaneh Rahmani, Elham Rayzan, Mohammad Reza Rahmani, Sepideh Shahkarami, Samaneh Zoghi, Arezoo Rezaei, Zahra Aryan, Mehri Najafi, Meino Rohlfs, Tim Jeske, Majid Aflatoonian, Zahra Chavoshzadeh, Fatemeh Farahmand, Farzaneh Motamed, Pejman Rohani, Hossein Alimadadi, Alireza Mahdaviani, Mahboubeh Mansouri, Marzieh Tavakol, Mirjam Vanderberg, Daniel Kotlarz, Christoph Klein, Nima Rezaei
The product of ZAP70 gene, ZAP-70, is essential for T cell receptor (TCR) signal transduction and is expressed predominantly on natural killer cells and T cell (Chan et al. 2016). ZAP-70 deficiency is characterized by the absence of CD8 + T cells in the periphery, defective TCR signalling in CD4+ cells, and defective T cell tolerance induction, the latter being cited for autoimmune manifestations in these patients (Liu et al. 2017). Importantly, the presence of IBD in patients with ZAP70 mutation is associated with a leaky SCID phenotype with residual CD4 + T cell activity (Liu et al. 2017). Single nucleotide variants of ZAP70 have been found to affect IBD risk in some populations (Bouzid et al. 2013). Our patient had low CD8+ counts, recurrent thrush and a CD phenotype and unfortunately died due to complications of candidemia at 14 months old.