U01.02.011 Differentiation of T cells

T cells are a critical component of the adaptive immune system, responsible for identifying and eliminating infected or malignant cells. Their differentiation occurs through a series of steps, primarily in the thymus, leading to the formation of various subtypes with specialized functions.

T Cell Differentiation Pathway

Location	Process	Description
Bone Marrow	T Cell Precursor	T cell precursors are generated in the bone marrow.
Thymus	Selection Process	– Positive Selection: T cells that can bind self-MHC survive. – Negative Selection: T cells with high affinity for self-antigens undergo apoptosis or become regulatory T cells.
Lymph Node	Activation	Mature T cells migrate to lymph nodes for activation by antigens.

T Cell Differentiation Pathway

T Cell Subtypes

T Cell Type	Markers	Function	Cytokines Secreted
Cytotoxic T Cell (CD8+)	CD8	Kill virus-infected and neoplastic cells by inducing apoptosis.	IFN-γ, IL-2
Helper T Cell (CD4+)	CD4	Activate other immune cells, including B cells and macrophages.	IL-4, IL-5, IL-6, IL-10, IFN-γ
Th1	CD4, T-bet	Activate macrophages and cytotoxic T cells.	IFN-γ, IL-2
Th2	CD4, GATA3	Activate eosinophils; involved in allergic responses.	IL-4, IL-5, IL-10
Th17	CD4, RORγt	Induce neutrophilic inflammation.	IL-17, IL-21, IL-22
Regulatory T Cell (Treg)	CD4, CD25, FOXP3	Maintain tolerance and prevent autoimmunity.	IL-10, TGF-β, IL-35

T Cell Subtypes

Selection Processes

Positive Selection

Location: Thymic Cortex
Description: T cells expressing T cell receptors (TCRs) that can bind self-MHC on cortical epithelial cells survive.

Negative Selection

Location: Thymic Medulla
Description: T cells with high-affinity TCRs for self-antigens undergo apoptosis or differentiate into regulatory T cells. Tissue-restricted self-antigens are presented due to the action of the autoimmune regulator (AIRE). AIRE deficiency can lead to autoimmune polyendocrine syndrome type 1, characterized by conditions such as chronic mucocutaneous candidiasis and adrenal insufficiency.

Key Interactions

Macrophage-Lymphocyte Interaction

Th1 cells secrete IFN-γ, enhancing monocyte and macrophage functions.
Interaction between T cell CD40L and CD40 on macrophages activates lymphocytes through antigen presentation.

Cytotoxic T Cell Function

Mechanism: Kill infected and malignant cells by inducing apoptosis.
Mechanism of Action: Release cytotoxic granules containing perforin and granzyme B.
CD8 Binding: CD8 binds to MHC I on virus-infected cells.

Regulatory T Cell Function

Role: Help maintain immune tolerance by suppressing effector T cell functions.
Markers: Identified by CD3, CD4, CD25, and FOXP3.
Activated Tregs secrete anti-inflammatory cytokines (e.g., IL-10, TGF-β).
IPEX Syndrome: Genetic deficiency of FOXP3 leads to autoimmunity and manifests as enteropathy, endocrinopathy, and dermatitis.

Points to Remember

T cell differentiation occurs in the thymus, involving both positive and negative selection processes.
CD8+ T cells are crucial for cytotoxicity, while CD4+ T cells are essential for helper functions.
Regulatory T cells play a vital role in maintaining immune tolerance and preventing autoimmunity.
AIRE deficiency is linked to autoimmune diseases, emphasizing the importance of proper T cell selection.

Bibliography

Janeway, C. A., et al. (2005). Immunobiology: The Immune System in Health and Disease. 6th edition. Garland Science.
Murphy, K., et al. (2016). Janeway’s Immunobiology. 9th edition. Garland Science.
Abbas, A. K., et al. (2014). Cellular and Molecular Immunology. 9th edition. Elsevier.

USMLE Step 1 Review Series

Curriculum

U01.02.011 Differentiation of T cells

T Cell Differentiation Pathway

T Cell Subtypes

Selection Processes

Positive Selection

Negative Selection

Key Interactions

Macrophage-Lymphocyte Interaction

Cytotoxic T Cell Function

Regulatory T Cell Function

Points to Remember

Bibliography

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