Th1 and Th2 Balance, Regulation, and Involvement in Disease
Cytokines are the hormonal messengers responsible for most of the biological effects in the immune system, such as cell-mediated immunity and allergic type responses. T lymphocytes are a major source of cytokines. These cells bear antigen-specific receptors on their cell surface to allow recognition of foreign pathogens. There are two main subsets of T lymphocytes, distinguished by the presence of cell surface molecules known as CD4 and CD8. T lymphocytes expressing CD4 are also known as helper T cells, and these are regarded as being the most prolific cytokine producers. This subset can be further subdivided into Th1 and Th2, and the cytokines they produce are known as Th1-type cytokines and Th2-type cytokines.
Type 1 helper T cells are characterized by the production of pro-inflammatory cytokines like IFN-γ, IL-2, and TNF-β. Th1 cells are involved in cell-mediated immunity. The cytokines produced by Th1 cells stimulate the phagocytosis and destruction of microbial pathogens.
Several chronic inflammatory diseases have been described as Th1 dominant diseases i.e. multiple sclerosis, diabetes, and rheumatoid arthritis.
Type 2 helper T cells are characterized by the production of IL-4, IL-5, IL-9, IL-10, and IL-13. Th2 cells are thought to play a role in allergy responses. Cytokines like IL-4 generally stimulate the production of antibodies directed toward large extracellular parasites. IL-5 stimulates eosinophil responses, also part of the immune response toward large extracellular parasites. Atrophy and allergy are thought to be Th2 dominant conditions.
Improved understanding of Th1 and Th2 differentiation will improve our overall understanding of the immune system, its response to infection and aberrant responses that lead to disease.
When Th1 cells produce IFN-γ, this prompts the macrophages to produce TNF and toxic forms of oxygen which destroy the microorganisms within the phagosomes and lysosomes. On the other hand, when Th2 cells produce IL-4 and IL-10, these cytokines block the microbe killing that is activated by IFN-γ.
The Th1/Th2 relationship has also been investigated in regards to transplantation. Th1 responses have been implicated in most forms of acute rejection and graft versus host disease, while Th2 responses have been variably associated with either protection or chronic rejection. However, cloned Th1 or Th2 cells have a similar capacity to reject skin grafts in experimental models, and regulatory T lymphocytes (Tr1/Treg cells) are now being implicated in protection and tolerance induction. The fetus is also analogous to an allograft and Th2 or Treg responses are thought to be protective, while Th1 responses may lead to resorption or spontaneous abortion.