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The balance between memory and effector CD4+ T Cells 1

Ghanage Manimaran 11N

As we grow older, signalling via T-cell antigen receptors (TCR) reduces. Signalling is the process in which TCR recognise the antigen on the surface of a cell and converts this into a chain of reactions that transmits cell signals to targets inside the cell However, the CD4+ T cells from older adults differentiate into effector cells rather than memory cells. The balance of different proteins (IL2Rα, and STAT5) affects the age of the aging gene in CD4+ T cells.

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T cells are a subset of lymphocytes and can be narrowed down to 3 types of lymphocytes: cytotoxic CD8+ T cells, helper CD4+ T cells and regulatory CD4+ T cells. The protein on the surface of the T-cell helps differentiate between them. There are many subsets of CD4+ T cells and the main functions include having the ability to coordinate the immune response for pathogens inside and outside the body by producing cytokines, a protein which act as chemical messengers and can destroy pathogens. Memory CD4+ T cells are useful in maintaining a person ’ s immunity, so if the bacteria re-enter the body, a faster, sooner, and stronger immune response is produced

Ageing is linked to a reduced immune response to diseases and vaccines. This is because there are fewer white blood cells capable of responding to new antigens and T cells take longer to respond to the antigens. This is reflected by the figures, the number of deaths has increased per year in old people, especially from viruses like influenza and COVID. The thymus produces less T cells as we grow older. The difference between the TCR signals has caused scientists to investigate the balance between effector and memory CD4+ T cells

Scientists found that TCR signalling is reduced in CDR4+ T cells and differentiates into more effector cells than memory cells. They also found that chromatin (the material that chromosomes are made of) accessibility was higher in adults and changes in response to TCR activation. After further investigation, it was discovered that the transcription factor STAT5 affects chromatin accessibility and transcription in CD4 T+ cells. This was presented by peaks in graphs for STAT5 which showed greater chromatin accessibility in CD4 T+ cells in adults. STAT5 is a protein which allows rapid delivery of signals from the membrane to nucleus.

It works alongside other transcription factors to regulate the expression of genes, in this case, the age-sensitive gene coding for the CD4+ T cells. Furthermore, the protein IL2Rα was also expressed more. The inhibition of IL-2Rα and STAT5increased the tendency of CD4+ T cells to differentiate into short-lived effector cells than memory cells.

The inhibition of IL-2Rα and STAT5increased the tendency of CD4+ T cells to differentiate into short-lived effector cells than memory cells.

Therefore, both these findings show that IL-2Rα and STAT5change the balance of CD4+ T cells in adults so that more effector cells are produced than memory cells.

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2. Pathways of Intracellular Signal Transduction - The Cell - NCBI Bookshelf (nih.gov)

3. Signal transduction by the T cell antigen receptor - PubMed (nih.gov)

4. The role of Stat5a and Stat5b in signaling by IL-2 family cytokines - PubMed (nih.gov)

5. Tipping the balance in CD4+ T cells | Nature Immunology

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