Learning Objective

Understand how T cells differentiate from precursors into CD4⁺ and CD8⁺ subsets, the cytokines driving CD4⁺ T-helper subset development, their secreted mediators, key functions, and the principles of thymic positive and negative selection.

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Origin & Development

Bone marrow: T-cell precursors arise.

Thymus: Maturation and selection.

• Cortex: Positive selection
• Medulla: Negative selection

Peripheral blood / Lymph node: Final differentiation into effector subsets.

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Thymic Selection (VERY Step 1 High Yield)

Positive Selection – Thymic Cortex

• Ensures T cells recognize self-MHC (but not too strongly).
• Double-positive (CD4⁺CD8⁺) thymocytes that bind self-MHC receive survival signals.

Negative Selection – Thymic Medulla

• Removes T cells that bind too strongly to self-antigens.
• Prevents autoimmunity.
• AIRE (Autoimmune Regulator) promotes the expression of peripheral antigens.
• AIRE deficiency → Autoimmune Polyendocrine Syndrome:
  • Chronic mucocutaneous candidiasis
  • Hypoparathyroidism
  • Adrenal insufficiency
  • Recurrent Candida infections

 

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Activity

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T-Cell Differentiation Pathway

T-cell precursor → Thymus

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Double-positive (CD4⁺CD8⁺) thymocyte
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After selection → CD4⁺ T helper cells & CD8⁺ Cytotoxic T cells

 

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Activity

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CD4⁺ T-Helper Cell Subsets (Cytokine Signals → Subset → Secretions → Function)

Th1 Cells

• Induced by: IFN-γ, IL-12
• Secretes: IFN-γ, IL-2
• Function:
  • Activate macrophages
  • Activate CD8⁺ cytotoxic T cells (cell-mediated immunity)
• High-yield: Important for intracellular pathogens (TB, viruses).

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Activity

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Th2 Cells

• Induced by: IL-2, IL-4
• Secretes: IL-4, IL-5, IL-6, IL-10, IL-13
• Function:
  • Activate eosinophils
  • Promote IgE class switching (allergic response, parasitic immunity)

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Th17 Cells

• Induced by: TGF-β, IL-1, IL-6
• Secretes: IL-17, IL-21, IL-22
• Function:
  • Recruit and activate neutrophils
  • Mucosal immunity
• Step 1 tie-in: Deficiency → chronic mucosal infections (e.g., Candida, Staph).

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Treg Cells (Regulatory T cells)

• Induced by: TGF-β, IL-2
• Secretes: TGF-β, IL-10, IL-35
• Function:
  • Maintain self-tolerance
  • Prevent autoimmunity
  • Suppress overactive immune responses

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CD8⁺ Cytotoxic T Cells

• Activated by Th1 cytokines (IL-2).
• Kill virus-infected and tumor cells using:
  • Perforin (creates pores)
  • Granzymes (trigger apoptosis)

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Activity