Identification of CTLA-4-Positive Cells in the Human Tonsil

Abstract

CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was originally defined as a T-lymphocyte antigen and was used as a target in cancer immunotherapy. Unfortunately, the existence of CTLA-4 in cells other than T-lymphocytes is often overlooked. The goal of the present study was to analyze the distribution pattern of CTLA-4 in the human tonsils using a panel of anti–CTLA-4 antibodies of different clones. We found that CTLA-4 was expressed in T-lymphocyte cells of various geneses, including hematopoietic cells and their derivatives (monocytes, macrophages, dendritic, plasma cells, mast cells, and neutrophils), as well as stromal cells of mesodermal (mesenchymal) origin and reticular epithelial cells of ectodermal origin. The expression of CTLA-4 in cells of different origins supports the proposition that CTLA-4 is not restricted to the lymphoid cell lineage and can provide broader effects of CTLA-4 on immune regulation.

Expression of CD38 in Mast Cells: Cytological and Histotopographic Features

“…At the same time, the question of the specificity of the antibodies used remains fundamental since the different efficacies of antibodies clearly arises due to their affinity for various epitopes of the CD38 molecule. The importance of this fact in the context of multiplex immunohistochemistry is evidenced by the results of our previous work, which showed the unequal efficiency of CTLA-4 detection using various antibodies [32]. Our results showed both differences in detecting CD38 in MCs, depending on the antibodies used, and different intensities of exoenzyme expression.…”

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

“… 134 , 135 – 138 While CD28 was found to be a T-cell costimulatory molecule, 139 CTLA-4 was later discovered to mimic CD28 and act as a brake on T-cell activation. 140 , 141 Under physiological conditions, CTLA-4 and CD80/CD86 binding can inhibit T-cell activation signals and prevent autoimmune disease. 142 , 143 Blocking CTLA-4 can directly target inhibitory signals on effector T cells and reduce the inhibitory effect of Tregs, 33 , 144 – 147 thus effectively enhancing the antitumor effect of T cells.…”

Immune Tolerance in the Oral Mucosa

“…CTLA-4 was originally defined as a T-lymphocyte antigen, and its expression in other cell types was overlooked for many years. However, a recent study demonstrated that stromal cells and reticular epithelial cells from human tonsils express this protein too, suggesting a broader effect of CTLA-4 on immune regulation and tolerance [85]. Interestingly, neoplastic characters of head and neck cancers (HNSCC) seem to mimic the molecular profile of epithelial cells.…”