What is the difference between T helper 1 (TH1) cells and T helper 2 (TH2) cells?

TH1 vs TH2 Cells: Key Differences and Functions

TH1 and TH2 cells are functionally distinct CD4+ T helper cell subsets that orchestrate different immune responses through their unique cytokine production patterns, with TH1 cells primarily driving cellular immunity against intracellular pathogens while TH2 cells mediate humoral immunity and allergic responses.

Fundamental Differences

Cytokine Production

• TH1 cells:

  • Produce interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-beta (TNF-β) 1, 2
  • These cytokines activate macrophages and promote cell-mediated immunity

• TH2 cells:

  • Produce interleukin-4 (IL-4), IL-5, IL-9, IL-10, and IL-13 1, 2
  • These cytokines stimulate B cell proliferation, antibody production, and eosinophil recruitment

Primary Functions

TH1 Cells

• Drive type-1 immunity characterized by intense phagocytic activity 2
• Mediate protection against intracellular pathogens (viruses, bacteria) 1
• Activate macrophages and cytotoxic T cells 3
• Responsible for delayed-type hypersensitivity reactions 4
• Contribute to elimination of cancerous cells 4

TH2 Cells

• Drive type-2 immunity characterized by high antibody titers 2
• Provide excellent helper function for B cell antibody production, particularly IgE 5
• Mediate protection against extracellular pathogens, especially parasites 1
• Promote eosinophil proliferation, differentiation, and activation via IL-5 5
• Support tolerance of xenografts and the fetus during pregnancy 4

Pathophysiological Roles

TH1 Dominance

• Associated with autoimmune disorders like multiple sclerosis and thyroid autoimmunity 1
• When poorly effective or excessively prolonged, may result in host tissue damage 1
• Important for eradicating infectious agents hidden within host cells 1

TH2 Dominance

• Associated with allergic diseases and certain autoimmune conditions like systemic lupus erythematosus 1
• Implicated in atopic disorders where allergen-specific TH2 cells induce IgE production via IL-4 5
• May be considered part of a regulatory mechanism to limit potentially harmful TH1 responses 1

Regulation and Balance

• TH1 and TH2 responses can reciprocally inhibit each other 4
• Imbalance between TH1 and TH2 cells can contribute to various pathological conditions 6
• In allergic rhinitis and asthma, an imbalance favoring TH2 cells plays an important role in IgE synthesis and inflammatory cell recruitment 6
• Environmental factors, antigen dose, and cytokine milieu during antigen presentation influence TH1/TH2 polarization 1, 7

Clinical Implications

• Modulating the TH1/TH2 balance has therapeutic potential for various immunological disorders 1
• In cancer immunotherapy, shifting allergen-specific CD4+ T cells from a TH2 to an "anergic" TH2 phenotype may be beneficial 6
• Effective immunotherapy in allergic conditions is associated with elimination of pathogenic TH2A subsets 6
• TH1/TH2 balance can be influenced by various factors including nutrients, hormones, and certain medications 4

Recent Advances

• A distinct pathogenic memory TH2 subpopulation (TH2A) has been identified in atopic subjects, characterized as terminally differentiated CD4+ T cells coexpressing specific markers 6
• Volatile anesthetics can affect TH1/TH2 balance, with different anesthetics producing varied effects on these cell populations 6

Understanding the TH1/TH2 paradigm provides crucial insights into immune regulation and offers potential targets for therapeutic intervention in various immunological disorders.