Induction of antigen-independent T cell proliferation in vitro

Abstract

Innate immunity is the first line of defense of the body against pathogens and it responds in a nonspecific way to all threats. Some of its major responses are inflammation and antiviral defense, which overall help to prevent, control, and eliminate infections. It also allows the induction of an adaptive immune response, which is determinant to prevent re-infection. The adaptive immune response depends on antigen recognition, it triggers stimulation signals that In vivo induce T lymphocytes to proliferation response in addition to cytokine production and a modification to the pattern of expression of cell surface glycoproteins. T lymphocytes are one of the effector cells on the adaptive immune response. Their function of destroying the pathogens and their toxic molecules have made them popular for the development of cell therapies, for example, the CAR T cell therapies, which are based on modifying the antigen receptors of the T cells to allow them to detect and destroy cancer cells. Therefore, mimic in vitro as much as possible in vivo stimulation to induce cell proliferation is key to improve cell therapy manufacturing, decrease the time of production and costs. In this work, different stimulation protocols with PMA, ionomycin, IL-2, and Dynabeads™ were tested and evaluated in terms of proliferation induction, and progression in the cell cycle, changes in the expression of surface proteins, and gene transcription levels of relevant genes. A correct overexpression of activation markers, as well as cytokines transcription, is confirmed, however, the stimuli were not correct to induce a significant increase in cell proliferation, and contrary to expected, it seems that induced cells to apoptosis.