T Cells Plead for Rejuvenation and Amplification; With the Brain’s Neurotransmitters and Neuropeptides We Can Make It Happen

Abstract

T cells are essential for eradicating microorganisms and cancer and for tissue repair, have a pro-cognitive role in the brain, and limit Central Nervous System (CNS) inflammation and damage upon injury and infection. However, in aging, chronic infections, acute SARS-CoV-2 infection, cancer, chronic stress, depression and major injury/trauma, T cells are often scarce, exhausted, senescent, impaired/biased and dysfunctional. People with impaired/dysfunctional T cells are at high risk of infections, cancer, other diseases, and eventually mortality, and become multi-level burden on other people, organizations and societies. It is suggested that “Nerve-Driven Immunity” and “Personalized Adoptive Neuro-Immunotherapy” may overcome this problem. Natural Neurotransmitters and Neuropeptides: Glutamate, Dopamine, GnRH-II, CGRP, Neuropeptide Y, Somatostatin and others, bind their well-characterized receptors expressed on the cell surface of naïve/resting T cells and induce multiple direct, beneficial, and therapeutically relevant effects. These Neurotransmitters and Neuropeptides can induce/increase: gene expression, cytokine secretion, integrin-mediated adhesion, chemotactic migration, extravasation, proliferation, and killing of cancer. Moreover, we recently found that some of these Neurotransmitters and Neuropeptides also induce rapid and profound decrease of PD-1 in human T cells. By inducing these beneficial effects in naïve/resting T cells at different times after binding their receptors (i.e. NOT by single effect/mechanism/pathway), these Neurotransmitters and Neuropeptides by themselves can activate, rejuvenate, and improve T cells. “Personalized Adaptive Neuro-Immunotherapy” is a novel method for rejuvenating and improving T cells safely and potently by Neurotransmitters and Neuropeptides, consisting of personalized diagnostic and therapeutic protocols. The patient’s scarce and/or dysfunctional T cells are activated ex vivo once by pre-selected Neurotransmitters and/or Neuropeptides, tested, and re-inoculated to the patient’s body. Neuro-Immunotherapy can be actionable and repeated whenever needed, and allows other treatments. This adoptive Neuro-Immunotherapy calls for testing its safety and efficacy in clinical trials.

Autoimmune Epilepsy - Novel Multidisciplinary Analysis, Discoveries and Insights

“…Normal healthy T cells are required for proper brain function (97,98,101,96,99). Indeed, T cells are needed for: cognition, spatial learning and memory, and adult neurogenesis (158)(159)(160)(161).…”

“…Indeed, T cells are needed for: cognition, spatial learning and memory, and adult neurogenesis (158)(159)(160)(161). T cells are also needed in brain for neuroprotection, for decreasing secondary neuronal degeneration, for increasing neuronal survival and regeneration after CNS injury, and for limiting CNS inflammation and damage upon injury and infection (97,98,101,96,99). In addition to the beneficial roles of T cells in the healthy brain, their presence and activity in neurological diseases requires a different and updated approach, in light of the findings of recent years.…”

“…First, normal beneficial T cells are needed for normal brain function ( 97 , 98 , 101 , 96 , 99 ), and have beneficial roles in various neurological diseases, ranging from tissue protection to regeneration [for review see ( 101 ), and for short summary see Part 12.1 below]. Thus, the presence of normal T cells in the brain is, or can be, in normal conditions, beneficial, not necessarily detrimental, as commonly assumed.…”

“…Second, T cells, alike neural cells, express most if not all these Neurotransmitter receptors ( Table 3 ), and can be affected, either activated or suppressed, directly by some of the respective Neurotransmitters. We study this scientific and clinical topic for many years, gave it the name ‘Nerve-Driven Immunity ’, and discuss it in many original papers, reviews, book, and international meetings named ‘Nerve-Driven Immunity’ [see for example ( 105 , 106 , 100 , 112 , 99 )]. In addition, the effects of Neurotransmitters on T cells are being studied by other researches worldwide, and some exciting findings were revealed in recent years.…”

“…Interestingly, partial support of our hypothesis, that T cells may be damaged in Autoimmune Epilepsy, comes from a recent relevant discovery that patients with NMDAR encephalitis, having NMDA-NR1 antibodies, have significantly lower frequencies of CD154-expressing NR1-reactive helper T cells than healthy controls, and produce significantly less inflammatory cytokines ( 52 ). Are normal T cells, which are beneficial and necessary for the proper functioning of both the immune system and the nervous system ( 97 , 98 , 101 , 96 , 99 ), indeed damaged in patients with several neurological diseases (specified in Table 3 ), as a result of the destruction of the T cells by the patient’s own autoimmune antibodies, which target the Neurotransmitter receptors which T cells express ( Table 3 ), alike neural cells do? To the best of our knowledge, this novel question has not yet been addressed.…”