T-cell development begins with haematopoietic stem cells in the bone marrow, which develop into pre-T lymphocytes that migrate to the thymus for maturation. In the thymus, thymocytes proliferate and differentiate through various stages defined by CD4 and CD8 co-receptor expression, progressing from double-negative to double-positive stages. The maturation process involves TCR gene rearrangement and selection processes that lead to the formation of functionally distinct mature T cells.
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5.2 T Cell Development and Maturation
T-cell development begins with haematopoietic stem cells in the bone marrow, which develop into pre-T lymphocytes that migrate to the thymus for maturation. In the thymus, thymocytes proliferate and differentiate through various stages defined by CD4 and CD8 co-receptor expression, progressing from double-negative to double-positive stages. The maturation process involves TCR gene rearrangement and selection processes that lead to the formation of functionally distinct mature T cells.
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T-cell development
& maturation
Dr. Ashish Kumar Singh 23
T-cell development The T lymphocytes are derived from haematopoietic stem cells of bone marrow.
The lymphocyte progenitor cells develop into
pre-T lymphocytes.
The pre-T lymphocytes leave the bone marrow
and enter the thymus for maturation.
Dr. Ashish Kumar Singh 24
Dr. Ashish Kumar Singh 25 T-cell development & maturation T-cell travel from the bone marrow through the blood to the thymus under the influence of chemotactic factors that are secreted by the thymic epithelial cells. In the thymus T cell known as thymocytes, In thymus T cells proliferates and differentiate along the development pathways that generate functionally distinct subpopulation of mature T cells. T cell maturation in the thymus is a complex multistep process.
Dr. Ashish Kumar Singh 26
T-cell development & maturation Stages of development can be defined broadly by the expression of the co-receptor CD4 and CD8. The most immuature thymocytes express neither coreceptor and are referred to as CD4- CD8- (double –negative DN) stage.
The progress to the CD4+ CD8+ (double –
positive DP) stage, which in turn to the CD4+CD8- or CD4- CD8+ (single positive or SP) stage.
Dr. Ashish Kumar Singh 27
T-cell development & maturation Double Negative progress through four stage of development (DN1-DN4) based on the presence or absence of cell surface molecules c-Kit (CD117), the receptor for stem cell growth factor CD44, an adhesion molecule CD25, the α chain of the IL-2 receptor. During the development process, they begin to rearrange their T cell receptor (TCR) gene loci.
Dr. Ashish Kumar Singh 28
Dr. Ashish Kumar Singh 29 T-cell development & maturation DN1 stage: TCR gene present in germ line (donot express TCR) DN2 stage: The gene for the TCR γ, δ, and β chain begin to rearrange. DN3: Rearrangement continued Decision has been taken in t-cell development whether to join the TCRγδ or TCRαβ T cell lineage DN4: Rearrangement of TCRα chain gene completed Dr. Ashish Kumar Singh 30 Dr. Ashish Kumar Singh 31 T-cell development & maturation During the transition between the DN4 and DP stage: Expression of TCRαβ heterodimer occurs in the CD4+ CD8+ double positive cells. Double positive cells will under negative and positive thymic selection in thymic cortex. DP cells under that successfully undergo selection go on to mature CD4+ or CD8+ T cell, which are single positive SP cells. Small population of DP cells give rise to other T cells including NKT cells and regulatory T cell. Dr. Ashish Kumar Singh 32
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