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T Cells:Regulation and Cellular Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
T cells develop from the population of immature precursors which represent only 2–3% of the total number of cells within the thymus. Thymocytes differentiate through a series of steps defined by the expression of surface molecules and interactions with other cells. These patterns of surface expression reflect a genetic program which is modified by external signals mediating the selective processes shaping the T cell repertoire. The most immature thymocytes are CD7+. The next marker to be expressed is CD2. CD2 is an adhesion molecule, it is important in direct cellular contacts between T cells and other cells participating in immune responses (see below and Chapter 10). Subsequently, thymocytes express CD1 (unknown function). At this stage of development these cells are called double-negative since they express neither the CD4 nor CD8 antigens.
Thymus Influence on Differentiation and Functional Maturation of T Lymphocytes
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
An alternative way of T cell activation involves the triggering of CD2 surface molecule. Three distinct epitopes were found to be present at CD2 as indicated by means of monoclonal antibodies. CD21 epitope is associated with sheep erythrocyte binding site, and rosette formation by T cell is blocked by respective monoclonal antibody. The remaining CD22 and CD23 epitopes are not involved in rosette formation, but the binding of antibodies to these epitopes resulted in clonal proliferation and IL-2 production within antigen specific MHC-restricted T cell clones. In this respect, alternative activation of clonal T cell expansion by triggering CD2 structures appeared to be analogous to that resulted from CD3-Ti stimulation. There are two important features of the CD2 pathway; the first is that CD2 triggering is macrophage and IL-1 independent, and the second is that CD3-Ti triggering is inhibitory for the alternative pathway of CD2 activation.84,86 Nevertheless, the presence of CD2 molecule is preserved at all the subsequent stages of thymocyte development and peripheral T lymphocyte functioning. Although we do not know the native ligand for CD2, thymic hormones or intrathymic localized cell surface structures can be considered in this respect, as well as the extrathymic activity of the thymic hormones.
Signaling to and from T Cell Integrins
Published in Yoshikazu Takada, Integrins: The Biological Problems, 2017
Subsequent studies extended these observations on αLβ2 upregulation in three important ways. First, αLβ2 functional activity was also shown to be upregulated by pairs of MAbs specific for the CD2 molecule.79 These results were consistent with earlier studies clearly demonstrating that such pairs of CD2-specific MAbs are capable of activating T cells.80 Second, in addition to upregulating αLβ2 activity, PMA, CD3 cross-linking, and mitogenic pairs of CD2 MAbs were subsequently shown to also upregulate the functional activity of α4β1, α5β1, and α6β1 on human CD4+ T cells20,65 as assessed by T cell adhesion to FN (via α4β1 and α5β1) and LN (via α6β1). These studies demonstrated that these activation signals coordinately upregulate multiple integrins expressed on the T cell surface. Furthermore, the use of purified ligands or differential antibody blocking has demonstrated that α4β1 adhesion to VCAM-1 and αLβ2 adhesion to ICAM-2 are also activation dependent.33,81,82 Third, the greater expression of integrins on human memory T cells is associated with increased memory T cell adhesion to integrin ligands such as ICAM-1, FN, and LN.20,65 The greater adhesion of memory T cells to integrin ligands compared to naive T cells was observed with both resting cells and cells activated by PMA, CD3 cross-linking, or CD2 MAbs.
Akt Phosphorylation Orchestrates T11TS Mediated Cell Cycle Arrest in Glioma Cells
Published in Cancer Investigation, 2021
Sagar Acharya, Sirshendu Chatterjee, Suhnrita Chaudhuri, Manoj Kumar Singh, Debanjan Bhattacharya, Malabika Bhattacharjee, Anirban Ghosh, Swapna Chaudhuri
Secreted glioma antigens pass through the blood–brain barrier (BBB) and, upon reaching the peripheral immune system specifically sensitize some lymphocytes against glioma. But, glioma cells also secrete immunosuppressive factors, making the peripheral immune system anergic (57). Our studies found that all the phenotypic and functional activities of all the immune cells within the peripheral and intracranial glioma environment are severely downregulated, helping unhindered glioma growth. Upon administration of isolated and purified T11TS in glioma-bearing rats, the scenario changed. The CD2-T11TS interaction on immunocytes activates the immune system. The activated lymphocytes enter the nearest lymph node, cross-talk with the antigen-presenting cells (APCs), thereby secreting inflammatory (Th1) cytokines helping the proliferation of lymphocytes (57). These activated CD4 and CD8 lymphocytes upon entering the brain cross-talk with the microglia (46,58). Activated macrophages and polymorphonuclear (PMN) cells also enter the brain. Lymphocytes execute glioma destruction through cytotoxicity (59). The macrophages, PMN cells, and microglia kill through phagocytosis (10).
Long-term efficacy and safety of botulinum toxin treatment for cervical dystonia: a critical reappraisal
Published in Expert Opinion on Drug Safety, 2021
Luca Marsili, Matteo Bologna, Joseph Jankovic, Carlo Colosimo
Other possible reasons for dropout from longitudinal studies were primary/secondary non-response, noted in up to 39% of withdrawn patients. In particular, Ramirez–Castaneda and Jankovic [35] found that the primary/secondary non-response was reported in 26.1 and 13.4% of patients, respectively, in a retrospective study [49]. Colosimo and colleagues in the INTEREST IN CD2 study [34] reported lack of effectiveness in 10 out of 1050 enrolled patients at baseline. Jochim et al. [46] reported a primary/secondary non-response in 12 and 5 out of 135 patients treated with onaBoNT-A, respectively; whereas it was of 5 and 18 out of 209 patients treated with aboBoNT-A, respectively. Other, less frequent, AEs which rarely lead to discontinuation of BoNT treatment include injection and post-injection pain and flu-like syndrome [50]. The latter condition that may occur in between 1.7 and 20% of patients treated with various preparations of BoNT-A and in up to 55% of those treated with BoNT–B, usually lasts only a few hours or days and may be associated with increased interleukins, particularly inducible protein [50]. Finally, other possible reasons for withdrawal include lack of adequate symptom improvement and difficulties accessing the treatment because of financial and/or logistical reasons.
Type 1 diabetes: key drug targets and how they could influence future therapeutics
Published in Expert Opinion on Therapeutic Targets, 2023
Yoon Kook Kim, Kashif M. Munir, Stephen N. Davis
Alefacept is a fusion protein of two leukocyte-function-associated antigen-3 molecules bound to IgG1. It binds CD2, expressed on CD4+ and CD8+ memory cells. These cells are thought to be primarily responsible for beta-cell destruction in T1DM. In a randomized, placebo-controlled, double-blind trial, 49 patients with recently diagnosed T1DM and confirmed the presence of DM-associated autoantibody were studied. Two 12-week courses of Alefacept (15 mg/week IM) showed improved preservation of C-peptide, lower insulin requirements (p = 0.002), and an approximately 50% reduction in severe hypoglycemic events (p = 0.001) compared with placebo. These benefits were seen 15 months after the last dose of alefacept, showing favorable sustained immunologic outcomes [22,23].