Differentiation and maturation of T cells
T cells complete the entire differentiation and maturation process in the thymus. Bone marrow stem cells reach the thymus with the blood, at this time called pre-T cells or thymocytes. Thymic stromal cells (such as thymic epithelial cells), 13 (2, Mq>, etc. can secrete thymosin, thymopoietin, thymic hormone and IL-7 and other cytokines, and express high levels of MHCI class, class â…¡ molecules, constituting the thymus Specific internal environment. Under the action of these hormones and cytokines and mediated by MHC molecules, pre-T cells are dependent on the thymus microenvironment and are genetically controlled to gradually mature and mature (Figure 2-2). At different stages of maturity, various membrane proteins can be expressed on the cell surface, such as CD4 molecules, CD8 molecules, T cell antigen receptors and CD3 molecules, etc., and have the functions of recognizing antigens, mediating specific immune responses and immune regulation. T cells The differentiation and maturation process is divided into three periods: double negative, double positive and single positive.
(1) Double negative phase: In the early stage of differentiation, T cells go through two stages, pro-Tcell and pre-Tcell. At this time, T cells neither express CD4 molecules nor CD8 The molecule is called a double negative T cell. T cells in the double negative phase do not express TCR and CD3 molecules, cannot recognize antigens and have no function.
(2) Double-positive phase: With differentiation and maturation in the thymus, double-negative T cells first express the p-chain of TCR (p-chain gene rearrangement first), and then express TCR. Chain precursor (pre-T2chain or pta, gp33), the TCR at this time is also called pre-TCR (pre-TCR or pTCR, consisting of pta and sound chain). The expression of pta and pTCR can promote the further differentiation of T cells and induce the activation of CD8 and CD4 molecular genes. T cells first express CD8 molecules. The appearance of CD8 molecules promotes the expression of CD4 molecules. CD4 molecules and CD8 molecules are simultaneously expressed to form double positive T cells. Double-positive T cells still cannot recognize the antigen and have no function.
During the differentiation and maturation of T cells, the expression of Lu chain is a major event that determines the fate of T cells. Once the p chain is expressed, it can be induced and promoted. The expression of the chain, thereby expressing the functional TCR, the T cells can continue to differentiate and mature; otherwise, the differentiation stops and eventually leads to the death of the T cells. Therefore, some people call this phenomenon TCR's pselection. Similarly, pta plays an important role in promoting TCR gene expression and T cell differentiation and maturation. If T cells cannot express pta and pTCR, the differentiation of T cells is blocked and they cannot further differentiate and mature. Apoptosis occurs and the clone is cleared. The expression of CD4 and CD8 molecules can further promote the expression of TCR and the differentiation and maturation of T cells. Experiments have confirmed that animals knocked out of the CD4 or CD8 gene cannot produce mature CD4- and / or CD8-T cells.
(3) Single-positive phase: T-cells in the double-positive phase undergo a secondary selection process in the thymus and differentiate into CD4 + T cells CD8 + T cells (referred to as CD4 T cells and CD8 T cells), that is, single positive T cells. This is a type of mature T cells that simultaneously express TCR and CD3 molecules, can recognize antigens, mediate immune responses and participate in regulating immunity. Once the T cells are mature, they leave the thymus with the blood flow and enter the peripheral immune organs or peripheral blood. In the differentiation and maturation of T cells, MHC molecules play an extremely important role. Experiments have confirmed that blocking MHCI class molecules or class II molecules with monoclonal antibodies cannot produce mature CD8T cells and / or CD4T cells.
Embroidery Cushion Cover,Cushion Cover Embroidery Design,Silk Embroidery Cushions,Embroidery Cushion Covers
Shenzhen Xinmingcai Clothing Co,.Ltd , https://www.xmcsz.com