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The Th1-Th2 model—what relevance to inflammatory arthritis?
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  1. PATRICK D W KIELY
  1. Department of Rheumatology, St George’s Healthcare NHS Trust, Blackshaw Road, London SW17 0QT

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    Just over a decade ago Mosmann and colleagues reported that murine T helper (Th) cell clones could be distinguished by distinct cytokine secretion patterns.1 Since then the concept of Th1 and Th2 subsets has become increasingly popular and the Th1-Th2 model represents one of the most important developments in our understanding of immunological processes in health and disease.

    The model encompasses two concepts derived from in vitro observations of longlived murine T cell clones: (1) CD4+ T cells may be classified into Th1 and Th2 subsets, based on the production of two functionally distinct profiles of cytokines. Th1 cells produce interferon γ (IFNγ), interleukin 2 (IL2), and tumour necrosis factor β (TNFβ), and in broad terms induce cell mediated immunity. Th2 cells secrete interleukins 4 (IL4), 5 (IL5), 6 (IL6), 10 (IL10), and 13 (IL13) and induce humoral and parasitic immunity. (2) Factors that stimulate the actions of one subset reciprocally inhibit the other subset, leading to a state of mutual antagonism. Thus IFNγ and interleukin 12 (IL12) stimulate Th1 cells and inhibit Th2 cells whereas IL4 stimulates Th2 cells and inhibits Th1 cells.

    More recently the original clear cut concept that the Th1-Th2 split may be applied to individual Th cells has evolved. Early observations from T cell clones demonstrated that single Th cells secrete either a pure Th1 or Th2 profile of cytokines. However, freshly isolated Th cells from antigen stimulated animals express a range of Th1 and Th2 cytokines (mRNA and protein) in a random distribution. This pattern has not been found to develop in individual cells in culture into the exclusive Th1 or Th2 pattern observed in clonal cells. Instead, the Th1 or Th2 characteristics of an in vivo immune response seems to be determined by a net shift in the secretion profile of …

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