Th1 cell

Th1 cells (Th1 cells stands for: T helper 1 cells) are a subgroup of CD4⁺ T helper cells that play a central role in the cell-mediated immune response. Th1 cells are essential for the defense against intracellular pathogens and the activation of the cell-mediated immune response. Th1 cells are considered to be the most important promoters of the delayed type hyersensitivity immune response. The Th1 response also serves to defend against tumors.

Th1 vs. Th2 balance: The ratio of Th1 to Th2 cells can vary according to the current defense situation, but in healthy people it is balanced and is also restored after activation of the immune system. Th1 and Th2 cells regulate each other: while Th1 cells are important for cellular immunity, Th2 cells promote the humoral immune response. An imbalance between these two subtypes can contribute to the development of infections, autoimmune diseases or cutaneous T-cell lymphomas. In organ-related autoimmune diseases, too, there is often an immune imbalance in favor of the Th1 cells.

In early mycosis fungoides, the tumor microenvironment consists mainly of Th1 cells, regulatory T cells and cytotoxic ^CD8+ T cells. Disease progression is defined by a shift from a Th1 phenotype to a Th2 phenotype.

A balanced and controlled immune balance is crucial to ensure an effective immune response without triggering autoimmune reactions.

The cytokine pattern of the Th1 phenotype: Th1 cells arise from naïve CD4⁺ T cells under the influence of interleukin-12 (IL-12) and interferon-γ (IFN-γ), which are mainly secreted by dendritic cells and macrophages.

Th1 cells mainly release interferon-γ (IFN-gamma), which:

• Activates macrophages and increases their phagocytic capacity
• Increases the expression of MHC class II molecules and costimulatory molecules
• Supports the differentiation of CD8⁺ cytotoxic T cells
• Enhances an inflammatory immune response

In addition, Th1 cells produce tumor necrosis factor-alpha (TNF-alpha) and IL-2(interleukin-2), which also contribute to the immune response:

• Combat intracellular pathogens such as Mycobacterium tuberculosis or Listeria monocytogenes
• Support of cytotoxic T cells in the destruction of infected cells
• Induction of increased macrophage activity for pathogen elimination

Significance of the Th1 cell in the immune defense: The Th1 immune reaction is characteristic of a cellular immune response through the cytokines: IF-gamma, TNF-alpha, IL- 2 and IL-12. IL-12 and IF-gamma promote the development of Th1 cells via the activation of the transcription factors STAT4 and STAT1 . INF-gamma activates macrophages, inhibits B cells and thus prevents a Th2 response. Macrophages promote the type 1 polarization of reactive T cells through their cytokine release (IL-12; TNF-alpha) and the production of NO. At the same time, macrophages intensify their effect as antigen-presenting cells (APC) and improve their antimicrobial ability against extra- and intracellular antigens.

1. Asadi-Samani M et al. (2017) Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review. Phytother Res 31:1128-1139.
2. Basu A et al. (2021) Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy. Front Immunol 12:669474.
3. Lee J et al. (2021) The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy. Front Immunol 12:625667.