The development of T lymphocytes

Dr. Glorivee Rosario Pérez

BIOL 4056

Parham P. (2009). The Immune System. Third Edition. Garland Publishing, New York.

The development of T cells in the thymus

T lymphocytes

Figure 7-2

T lymphocytes cont.

T cells lineages (develop in the thymus):

α:β T cells (majority)

γ:δ T cells (minority)

CD4

CD8

Thymus:

Is a lymphoid organ in the upper anterior thorax just above the heart.

It contains immature T cells (thymocytes), which are embedded in a network of epithelial cells (thymic stroma). These elements form:

Cortex

Medulla

The cellular organization of the thymus

Figure 7-8

Thymus development:

Birth – the human thymus is fully developed.

Puberty – increase in size.

Adult (30 years) – degeneration of the thymus.

B vs T cells

The bone marrow is continually turning over the B cell repertoire during the whole of person’s lifetime.

The thymus works principally during youth, when it serves to accumulate a repertoire of T cells that can then be used throughout life.

Two lineage of T cells:α:β and γ:δ

Maturation of thymocytes into mature T cell occurs in distinct stages. These are marked by changes in the status of the:

T-cell receptor gene.

expression of the T-cell receptor protein.

production of other T-cell surface glycoprotein: CD4, CD8 and CD3 complex.

Two lineage of T cells:α:β and γ:δ cont.

Progenitor Cells(no cell-surface glycoproteins)

Thymic stromal cells(epithelial cells)

Subcapsular region of the outer cortex

Progenitor Cells(Proliferate)

A week

T-cell express specific adhesion molecule : CD2No expression of : TCR complex, CD4, CD8, CD3

(double negative thymocytes: CD4-CD8-)

Two lineage of T cells:α:β and γ:δ cont.

Figure 7-24

Figure 7-25

Cells that fail to make productive

rearrangement die by apoptosis and are

phagocytosed by macrophages in the thymic cortex.

Two lineage of T cells:α:β and γ:δ cont.

Expression of CD4 and CD8

TCR α-chain genes

Positive and negative selection of the T-cell

repertoire

Positive selection : MHC

Is a process in the thymus that selects immature T cells with receptors that

recognize peptide antigens presented by self-MHC molecules.

Only cells that are positively selected are allowed to continue their maturation.

Positive selection : MHC cont.

Positive selection

takes place in the

cortex of the thymus.

Positive selection : CD4 and CD8 co-receptor

Single-positive thymocytes – double positive thymocytes mature into cells that express just one or other of the two co-receptors.

CD4+CD8+

CD4+CD8-

CD4-CD8+

Positive selection : CD4 and CD8 co-receptor cont.

α-chain genes

Negative selection

Process in the thymus whereby developing T cells that recognize self antigens are induced to

die by apoptosis.

Negative selection cont.

Mature T-cell

Thymus → secondary lymphoid tissue

Mature naïve T cell↓

Thymus ↓

Blood↓

Secondary lymphoid tissues

↓Lymph

↓Blood

Thymus → secondary lymphoid tissue cont.

Naïve T cells are activated by their specific antigens in T cell rich areas of secondary lymphoid tissues

↓Final phases of T cell development and

differentiation↓

The mature T cell divide and differentiate into effector T cells

CD8 T cells CD4 T cells (TH1/TH2)

↓Some stay in the lymphoid tissues while others

migrate to sites of infection

Additional information about T-cell

Bone marrow transplantation

Bone marrow transplantation cont.

Disease

Summary

Summary

Summary cont.

Summary cont.

Summary cont.

Summary cont.