PRAGYA SANTRA, AMITY UNIVERSITY
Genome-wide association studies (GWAS) mapped the T-cell stimulatory pathways along with the CD28, CTLA4, and ICOS genes. GWAS studies and autoimmune disorders identified enriched chromatin regions as a consequence of memory T-cell over-activation. T-cell stimulation after occurring in the secondary lymphoid delivers two signals, first via T-cell receptors (TCR) to recognize antigens binding to the perfect MHC molecule and the second via antigen-presenting cells (APCs) by upregulating costimulatory ligands.
T-cell expresses CD28 as the costimulatory receptor that interacts with CD80 and CD86 ligands on APCs. This coordination is necessary for T-cell activation, proliferation, differentiation, and survival. CD28 controls the check-points for T-cell activation. But the rate of activation varies in different immunological setup. CD80 and CD86 upregulate CD28 costimulation. In this regard, over-modulation of the CD28 pathway excites the T-cell activation pathway provoking the body’s immune system to become more sensitive towards any antigen. Thus, due to this over-activation, the T-cells start proliferating and attacking uncontrollably to the self-cells, resulting in autoimmunity.
Further studies revealed through both memory and naive T-cells are sensitive towards CD28 over-stimulation. Memory cells appear to be more responsive to CD28 signals. Once triggered, the memory T-cell division and proliferation even continue when CD28 engagement is blocked. It drives chromatin rearrangements affecting specific transcription factors targeting T-cell effector cytokines. This phenomenon becomes dangerous as the whole T-cell activation pathway is triggered, which even leads the immature T-cells to depart from the lymphoid organs and take part in the immune responses. Pieces of evidence revealed that decease in CD28 ligands resulted in further inhibition in the memory T-cells. The robust response is observed in T-memory cells during CD28 crosslinking and is unique to it. For the memory cells to be so over-reactive, even an encounter with any previously known antigen triggers the memory T-cells to overexcite.
Over-expressed memory and naive T-cells even operate different gene expressions in our body may lead to any immunological disorder. The phenomena of T-cell activations are the epi-center to autoimmune diseases. Controlled therapies and studies are required to put the effects under control. This process of over-activation of T-cells has hyped the connection between cancer and the same.
Also read: AMPEROMETRIC BIOSENSOR OF L-FUCOSE- FIRST SCREENING TEST OF CANCER?
SOURCE
Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation; Dafni A. Glinos, Blagoje Soskic, Cayman Williams, Alan Kennedy, Luke Jostins, David M. Sansom & Gosia Trynka; 23 November 2020; Genes & Immunity-Nature, doi: https://doi.org/10.1038/s41435-020-00118-0
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