A13 Mature of T-cells

Question 1

T-cell

Answer 1

• Progenitor cells are formed in the bone marrow
• Immature T-cells migrate to the thymus
• Receptors: αβ and γδ
• γδ T-cells migrate to the mucosa without to maturing in the thymus
• αβ T-cells mature in the thymus, many of them die
• Atg.-recognition: MHC restriction
• Cell-line marker: CD3

Question 2

T-cell Types

Answer 2

• Based on Receptor
– Conventional αβ T-cell
– γδ T-cell
– Non-conventional αβ NK cell (non-variable chains)
• Based on Function
– Effectors (cytotoxic, helper, regulatory)
– Memory T-cells

Question 3

Citotoxic T-cells (Tc)

Answer 3

• Cell surface marker
‒ CD3+
‒ CD8+
• Recognition of endogenous Atg presented through MHCI
• Protection against viral infections, tumors and intracellular pathogens

Question 4

T helper cells (Th)

Answer 4

• Cell surface marker
‒ CD3+
‒ CD4+
• Recognition of exogenous Atg presented through MHCII
• Mainly Th1, Th2 and inflammatory subtypes
• CK production to control the immune response
• Th17 enhances inflammation
• Regulator T-cells (Treg) decrease Atg-specific immune response

Question 5

γδT-cell

Answer 5

• The TCR (T-cell receptor) contains γ and δ chains
• Less known than classical αβ T-cells
• Migration to the periphery before or after reaching the thymus
• Present in the blood is small amounts
• Increased presence on the mucous membranes as intraepithelic lymphocytes (IEL)
• Atg recognition without MHC
• Reaction mainly to lipids→ tolerance

Question 6

MHC-dependent selection:

Answer 6

• Thymocytes rearrange their TCR-α chain loci, to produce an αβTCR.
• These cells then undergo positive selection in the cortex.
• They interact with self-antigens in the context of MHC class I or II.
• Those cells that engage antigen/MHC with an appropriate affinity survive, whereas those cells that interact with a weaker affinity die by apoptosis.
• Thymocytes then migrate to the medulla to undergo negative selection. They will presented self-antigens on APCs, such as macrophages and dendritic cells.
• Thymocytes that interact too strongly with antigen undergo apoptosis. The majority of developing thymocytes die during this process.
• Following selection, down-regulation of either co-receptor produces either naïve CD4 or CD8 single positive cells that exit the thymus and circulate the periphery.
• About 98% of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection, whereas the other 2% survive and leave the thymus to become mature immunocompetent T cells.

Question 7

Process

Answer 7

• Like B cells, all T cells originate from haematopoietic stem cells in the bone marrow.
• Atg-recognition: MHC restriction
• Cell-line marker: CD3

• The progenitor cells formed in the bone marrow migrate to and the thymus and expand by cell division to generate a large population of immature thymocytes.
• The developing progenitors within the thymus, also known as thymocytes, undergo a series of maturation steps that can be identified based on the expression of different cell surface markers. The majority of cells give rise to αβ T cells, but ca. 5% give rise to the γδ T cell receptor (TCR).
o γδ T-cells migrate to the mucosa without maturing in thymus
o αβ T-cells mature in the thymus (but many of them die)
• The earliest thymocytes express neither CD4 or CD8, and are therefore classed as (DN) doublenegative cells (CD4-CD8-).
• The DN population can be further subdivided by the expression of CD44 and CD25.
• Cells that lack expression of CD44, but express CD25 (DN3) undergo a process termed beta-selection. This process selects cells that have successfully rearranged their TCR-β chain locus.
• The cells will further express CD4 and CD8, and are then termed double positive (DP) cells (CD4+CD8+). • Cells that do not undergo beta-selection die by apoptosis.