Tc2 cells respond to soluble antigen in the respiratory tract and induce lung eosinophilia and bronchial hyperresponsiveness.
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-gamma 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-gamma) 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.
Sawicka
Elzbieta
E
Department of Immunology, Guy's King's and St. Thomas' School of Medicine, London, GB. ela.sawicka@pharma.novartis.com
Noble
Alistair
A
Walker
Christoph
C
Kemeny
David M
DM
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D004802:Eosinophilia / Q000209:etiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000941:Antigens; D015847:Interleukin-4; D007371:Interferon-gamma