TH1 CD4(+) CELLS ADOPTIVELY TRANSFER EXPERIMENTAL HYPERSENSITIVITY PNEUMONITIS

Cultured cells from Micropolyspora faeni-sensitized donors can adoptiv ely transfer murine experimental hypersensitivity pneumonitis (EHP). T o determine whether the CD4(+) cells responsible for transfer have cha racteristics of Th1 or Th2 cells, we established cell lines from lung- associated lymph nodes of M. faeni-sensitized C3H/HeJ mice by culturin g with antigen and either IFN-gamma, IL2, and anti-IL4, or IL4. Cell l ines were stimulated regularly with antigen, fresh antigen-presenting cells, and the cytokine/anti-cytokine antibody cocktail. At various ti mes after initiation of culture, cells were injected intravenously int o recipients, which were then challenged intratracheally with M. faeni and sacrificed and the extent of pulmonary inflammatory response was determined. IFN-gamma, IL4, and IL10 levels were determined in superna tants of cell cultures stimulated with M. faeni to characterize the ce ll lines as Th1 (IFN-gamma, but low IL4 and IL10 secretion) or Th2 (IL 4 and IL10, but low IFN-gamma secretion). Cell lines were differentiat ed into either Th1 (IFN-gamma = 310 +/- 45 U/ml, IL4 = 0.10 +/- 0.1 U/ ml, ILIO = 1750 +/- 75 pg/ml, >99% CD4(+)) cell lines by Day 16 of cul ture or Th2 cell lines (IFN-gamma = 1.8 +/- 1.0 U/ml, IL4 = 830 +/- 38 8 U/ml, IL10 = 51,700 +/- 10,900 pg/ml, >96% CD4(+)) by Day 30. Th1 ce ll lines were able to adoptively transfer EHP whereas Th2 cell lines w ere unable to adoptively transfer EHP. The ability to transfer EHP was directly related to the amount of IFN-gamma and inversely to the amou nt of IL4 secreted by antigen-stimulated cells. We conclude that it is possible to produce CD4(+) cell lines with either Th1 or Th2 characte ristics from lung-associated lymph nodes of mice exposed to M. faeni a nd that only Th1 CD4(+) cell lines can adoptively transfer EHP. (C) 19 97 Academic Press.