PCB 3233 Chapter 7 2021 - 55 Final (1)

Chapter 7: Development Of T Lymphocytes

Overview of T Cell Development

• The process of T cell maturation primarily occurs in the thymus.

• The development involves:

  • Stages of gene rearrangement producing the primary repertoire of T-cell receptors (TCRs).

  • Positive and negative selection to refine the T-cell repertoire.

• Resulting mature T cells are naïve and ready to respond to infections.

Comparison of T and B Cell Development

• Similarities between T and B lymphocyte development:

  • Both derive from bone marrow stem cells.

  • Both undergo gene rearrangement to create antigen receptors.

• Differences:

  • B cells rearrange in the bone marrow; T cell precursors migrate to the thymus for rearrangement.

  • Formation of distinct T cell lineages:

    • α:β T cells (majority, only 1-2% exit thymus).

    • γ:δ T cells (less stringent selection).

Thymus as Primary Lymphoid Organ

• Major role:

  • Ensures T cells that leave are self-MHC restricted.

• Selection processes in the thymus:

  • Positive selection: Promotes survival of immature T cells recognizing self-MHC (non-autoreactive).

  • Negative selection: Induces death of autoreactive immature T cells (bind too strongly to self-MHC).

• Outcome: Mature T cell is tolerant to self-antigens yet responsive to foreign antigens.

T Cell Lineages and Development Stages

• Origin: T cells originate from bone marrow as stem cells, migrate to the thymus.

• Lineages:

  • Majority are α:β T cells.

  • Minority are γ:δ T cells.

• Development involves:

  • Expression of various cell-surface proteins (CD4, CD8).

  • Thymocytes undergo differentiation while interacting with thymic epithelial cells.

Cellular Organization of the Thymus

• Immature thymocytes are embedded in the thymic stroma composed of specialized epithelial cells.

• Macrophages in both cortex and medulla ensure removal of thymocytes that do not mature properly.

Thymic Anatomy and Function

• The thymus features:

  • Distinct cortical and medullary regions, with unique populations of epithelial and stromal cells.

  • Functions are crucial during embryonic development and ongoing T-cell maturation processes.

Positive and Negative Selection

• Positive Selection:

  • Occurs in the thymus cortex; T cells that bind moderately to self-MHC survive.

• Negative Selection:

  • T cells with high-affinity binding to self-antigens are eliminated, promoting central tolerance.

• Factors involved:

  • AIRE (Autoimmune Regulator) expresses self-peptides in the thymus for selection processes.

Regulatory T Cells and T Cell Functions

• Regulatory T cells (Tregs) arise from CD4 T cells, characterized by CD25 and FoxP3 expression.

• Tregs suppress the immune response to self-antigens, preventing autoimmune reactions.

Differentiation of T Cells in Secondary Lymphoid Tissues

• After selection in the thymus, mature T cells circulate to secondary lymphoid organs.

• Upon antigen encounter, T cells differentiate into various effector cells:

  • CD8 T cells → cytotoxic T cells.

  • CD4 T cells → TH1 or TH2 helper T cells, influenced by cytokines and the nature of the immune response.

Summary of T Cell Development Stages

• Stages of Development:

  • Double-negative (DN) thymocytes proliferate in subcapsular region.

  • Double-positive (DP) thymocytes undergo positive selection in the cortex.

  • Single-positive mature T cells exit the thymus into circulation.