Type 1 T helper and type 2 T helper cells: functions, regulation and role in protection and disease

Abstract

Two very distinct cytokine secretion patterns have been defined among murine CD4+ T cells. Type 1 helper (TH1), but not type 2 helper (TH2), cells produce interleukin (IL)-2, gamma-interferon (IFN-gamma) and tumour necrosis factor-beta, whereas TH2, but not TH1, cells express IL-4, IL-5, IL-6 and IL-10. The different cytokine patterns lead to different functions of the two types of T cell. In general, TH2 cells are excellent helpers for B-cell antibody secretion, particularly IgE responses. On the other hand TH1 cells induce delayed-type hypersensitivity reactions. There is general agreement that the different functional subsets of TH cells arise post-thymically from a common pool of precursors and as a consequence of activation of antigen. However, the factors affecting differentiation of TH precursors into the TH1 or TH2 subsets are still unclear. Mutual cross-regulation between TH1 (via IFN-gamma) and TH2 (via IL-10) has also been reported. Recently, human T cell clones similar to murine TH1 and TH2 cells have been demonstrated. Most allergen- or helminthic antigen-specific CD4+ human T cell clones have a TH2 phenotype, whereas the majority of T-cell clones specific for mycobacterial antigens or antigens responsible for type IV hypersensitivity exhibit a TH1 phenotype. Human TH2 clones provide B-cell help for IgE synthesis, whereas most TH1 clones are cytolytic for antigen-presenting cells, including B lymphocytes. It is highly probable that the selective or preferential activation of CD4+ T-cell subsets secreting defined patterns of cytokines is of major importance in determining the class of immune effector function, thus influencing both protection and immunopathology.