Tc2 cells respond to soluble antigen in the respiratory tract and induce lung eosinophilia and bronchial hyperresponsiveness

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Abstract
The key role of T helper 2 (Th2) cells in asthma is well established. In contrast, the function of CD8+ T cells producing a distinct cytokine profile similar to Th2 cells is largely unknown. To analyze a potential role of CD8+ T cell subsets, allergen‐specific, in vitro‐differentiated T cytotoxic (Tc1 or Tc2) cells from T cell receptor transgenic OT‐I mice were adoptively transferred into naive C57BL/6 mice. Subsequent allergen challenge of mice injected with Tc1 cells (producing IFN‐γ but no IL‐4) resulted in a neutrophilic airway inflammation without induction of bronchial hyperresponsiveness (BHR). In contrast, the inflammatory response of recipients of adoptively transferred Tc2 cells (producing high levels of IL‐4 but little IFN‐γ) was characterized by significantly increased numbers of eosinophils and induction of BHR to methacholine. The response of antigen‐specific CD8+ T cells to soluble antigen was also observed in an in vitro system. A low concentration of antigen was shown to favor the generation of Tc2 cells, whereas high antigen load resulted in the differentiation of Tc1 cells. Thus, allergen‐specific Tc2 cells respond to inhaled soluble antigen, produce an inflammatory response qualitatively similar to Th2 cells and therefore may exacerbate the Th2‐driven airway inflammation in asthma.