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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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0% found this document useful (0 votes)
38 views10 pages

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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vorapallavi
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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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