Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy

Abstract

In human beings, as in mice, two distinct patterns of cytokine secretion have been defined among CD4 + helper T‐cell clones. Human type 1 helper (Th1), but not type 2 helper (Th2), cells produce interleukin‐2 (IL‐2), gamma‐interferon (IFN‐γ), and tumor necrosis factor‐β, whereas Th2, but not Th1, cells secrete IL‐4 and IL‐5, but not IL‐2 or IFN‐γ. Other cytokines, such as IL‐3, IL‐6, GM‐CSF, or TNF‐α, are produced by both Th1 and Th2 cells. The cells, a third Th subset, show combined production of Th1‐and Th2‐type cytokines. The different cytokine patterns are associated with different functions. In general, Th2 cells provide an excellent helper function for B‐cell antibody production, particularly of the IgE class. On the other hand, Th1 cells are responsible for delayed type hypersensitivity reactions and are cytolytic for autologous antigen‐presenting cells, including B cells. Most allergen‐ or helminth‐antigen‐specific human CD4 + T‐cell clones exhibit a Th2 phenotype, whereas most clones specific for bacterial antigens show a Th1 profile. Allergen‐specific Th2 cells seem to play a crucial role in atopy. These cells induce IgE production via IL‐4 and favor the proliferation, differentiation, and activation of eosinophils via IL‐5. In addition, Th2‐derived IL‐3 and IL‐4 are mast‐cell growth factors that act in synergy, at least in vitro. Recent evidence indicates that allergen‐specific Th2 cells are selectively enriched in tissues affected by allergic inflammation, such as the bronchial mucosa of subjects with allergic asthma. However, the reason why allergens preferentially expand Th2 cells in atopics is unknown. A number of factors may influence Th subset differentiation into Th1 or Th2 cells. At present, the IL‐4 produced in the microenvironment in which antigen is presented to Th cells seems to be the major factor favoring Th2 development. In this connection, the aberrant production of IL‐4 (and IL‐5) exhibited by T cells from atopics, even in response to bacterial antigens, may be of great importance. Copyright © 1992, Wiley Blackwell. All rights reserved