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• W4385211239 startingPage "31" @default.
• W4385211239 abstract "T cell is one of the most important cells involved in the pathophysiology and outcome of stem cell transplant (SCT). It governs many of the steps involved in pre-SCT, peri-SCT and post-SCT processes. It is very important to understand T cell development and function in detail before understanding transplant physiopathology. T cell’s journey begins from the bone marrow and ends in the peripheral tissues by either fighting the infections or permanently residing in the secondary lymphoid organs as memory T cell. Thymus plays the most important role in transforming a docile T cell precursor into a warrior. Qualitative or quantitative defects in T cells can lead to various inherited and acquired diseases. T cells and B cells have developed special mechanisms whereby they acquire the power to eliminate the infections and to remember them for a long time. How these cells acquire these extra powers to eliminate the antigen is a very interesting subject and its brief knowledge is essential as any defect in these mechanisms post-SCT can lead to T and B cell defects, thereby resulting in delay in immune reconstitution, and development of autoimmunity hence leading to increased risk of infections and graft versus host disease (GVHD), respectively. The recombinase-activating genes (RAGs) code for proteins that play important roles in the rearrangement of the genes that form T cell receptor (TCR) molecules. These RAG1 and RAG2 proteins initiate gene rearrangement in such a way that they can provide highly variable TCRs in the T cells developing in the thymus, so that each TCR can fit the an unique antigen perfectly, and since millions of antigens are present, the need for variability in TCR becomes necessity of T cells to counter million of infections. This generation of variability is termed broadening of T cell repertoire, and takes place in thymus. Since there are not as many genes as are antigens to which the immune system is exposed to, the ability of the adaptive immune system (which include T and B cells) to recognize millions of possible antigens is based on the fact that few genes can combine in various permutations and combinations to generate millions of different TCRs. This depends on combinatorial joining (joining of a given number of segments from a larger number of available options) of variable (V), diversity (D) and joining (J) gene segments that code for the antigen-binding regions of TCRs in T cells and B cell receptors (BCRs) in B cells. Other than RAG genes, another very crucial gene that modifies T cell function in the thymus is the AIRE (Auto-Immune Regulator) gene, which helps T cells to distinguish self from non-self antigens and hence provides a mechanism to identify and eliminate non-self antigens. T cell maturation in the thymus involves three main steps: TCR development (β selection), positive selection, and negative selection of T cells. The absence of RAG and AIRE genes cause severe T cell defects. T cells get damaged during SCT by the conditioning regimens, radiation and post-SCT immunosuppression leading to poor immune reconstitution. T cells are also crucial for donor stem cell engraftment and can lead to acute GVHD. Thymic is also prone to damage during SCT and this can delay the immune reconstitution and can also lead to development of chronic GVHD." @default.
• W4385211239 created "2023-07-25" @default.
• W4385211239 creator A5030108485 @default.
• W4385211239 date "2023-01-01" @default.
• W4385211239 modified "2023-10-16" @default.
• W4385211239 title "T Cell Development" @default.
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• W4385211239 doi "https://doi.org/10.1007/978-981-19-5802-1_4" @default.
• W4385211239 hasPublicationYear "2023" @default.
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