Developmental markers of T lymphocytes

Developmental markers of T lymphocytes:

·        Developing thymocytes pass through a series of distinct stages which are marked by changes in the expression of T cell receptor, cell-surface proteins such as the CD3, CD4, and CD8.

·        These surface markers reflect the maturation of the cell, and particular combinations of cell-surface proteins are used as markers for T cells at various stages of differentiation.

·        The early cell that is committed to become a T cell in the thymus expresses only the CD3 marker. Because they do not express CD4 or CD8 they are called 'double-negative' thymocytes or immature T cells.

·        After which, CD4 and CD8 are expressed by the same cell; these are known as 'double positive' thymocytes. These cells enlarge, divide and express low levels of T cell receptor.

·        Those cells whose receptors can interact with self-peptide and self-MHC molecular complexes lose expression of either CD4 or CD8 and increase the level of expression of the T-cell receptor. The outcome of this process is the 'single-positive' thymocytes, which, after maturation, are exported from the thymus as mature single-positive CD4 or CD8 T cells.

Function of helper T cells and cytotoxic T cells

·        T cells are critical in regulation, activation, and action of the adaptive immune system.

·        They are “born” in the bone marrow but “mature” in the thymus.

·        Within the thymus both positive and negative selection occurs, resulting in specialized T cells with different clusters of differentiation (CD) on their cell surface; the main cell types are CD4+ and CD8+ T cells.

CD4+ T Cells:

These “helper T cells” undergo further differentiation after appropriate stimulation by interleukins to become either Th1 or Th2 cells with specific functions to help regulate both the humoral and cell-mediated immune system.

Th1 cells:

·        Th1 cells are involved in the regulation of the cell-mediated response.

·        They are activated by APCs and secrete interferon-Y (IFN-Y), which activates antigen presenting cells (APCs) for efficient killing.

·        They also secrete IL-2, which activates CD8+ (cytotoxic T cells) to kill virally infected cells.

·        Another cytokine secreted by Th1 cells is TNF- ß, which activates macrophages, inhibits B cells, and is directly cytotoxic for some cells.

Th2 cells:

·        These cells are mainly involved in activating B cells.

·        They enhance isotype switching by secreting IL-4, IL-5, and IL-6.

·        They activate eosinophils and mast cells too.

·        They also secrete IL-10, which inhibits the development of Th1 cells and cytokine release from macrophages.

Development of Th1 and Th2 cells from CD4+ T cells: How does the CD4+ T cell decide in which subtype to develop? The answer to this is cytokines!

·        Exposure to IL-4 and IL-5 (also IL-9 and IL-13) favors the development of Th2 cells.

·        IFN-Y and IL-12 (and its relatives IL-23 and IL-27) favor Th1 cell development.

CD8+ T Cells:

Also known as cytotoxic T cells, these cells are responsible for seeking out and eliminating virus/parasite-infected cells, cancer cells, and other foreign cells.

·        They induce apoptosis in target cells.

·        They also release the cytokines IFN-Y, TNF -A, and TNF-ß, which contribute to host defense.

It is important to understand the main steps involved when viral antigen is taken up by an APC to the point at which CD8+ T cells are “seeking and destroying” the infected cells.

·        When an APC (mainly dendritic cell or macrophage) is exposed to viral antigen, it will load the antigen onto an MHC II for presentation to a CD4+ T cell. It will also express a co-stimulatory signal on its cell membrane (e.g., B7). The TCR can then interact with the antigen-positive MHC II on the APC.

·        A single signal is not enough for activation. The immune system’s checks and balances require a second signal for appropriate activation to occur. The B7 co-stimulatory signal on the APC must interact with CD28 on the CD4+ T cell while the TCR–MHC II interaction is occurring.

·        If these conditions are met, the CD4+ T cell will release IFN-γ to stimulate the APC to efficiently kill its pathogen. The CD4+ T cell will also release IL-2 to (1) cause activation and proliferation of CD8+ cytotoxic T cells to kill virally infected host cells, and (2) cause CD4+ T cell proliferation and differentiation in an autocrine manner.

Self-reactivity: What happens when a TCR recognizes and binds to host antigens? In a healthy individual, the way the immune system tackles this issue is by anergy, deactivating that self-reactive T cell. If this process fails, it could potentially lead to the development of an autoimmune disease.
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