The absence of IFN-gamma leads to increased Th2 responses after influenza A virus infection characterized by an increase in CD4+ but not CD8+ T cells producing IL-4 or IL-5 in the lung.
The cytokine IL-4 has been shown to be responsible for the switch of both CD4+ and CD8+ T cells to a Th2 or TC2 functional phenotype in vitro which both secrete IL-4 after stimulation. In contrast the presence of IFN-gamma interferes with the generation of Th2 and TC2 cells in vitro. Furthermore, it is well established that in the absence of IFN-gamma and the presence of IL-4 Th2 cells also develop in vivo. However, little is known about the conditions leading to the generation of TC2 cells in vivo. For this reason we investigated if Th2 and TC2 cells develop in the lung of IFN-gamma deficient mice which were infected with Influenza A virus. Surprisingly, we were only able to detect Th2 but not TC2 cells in the bronchoalveolar fluid and the mediastinal lymphnodes of IFN-gamma deficient mice infected with influenza A virus 1, 2 and 3 weeks by intracellular FACS staining for IL-4 or IL-5. In infected and uninfected wild type mice and uninfected IFN-gamma deficient mice we were not able to detect any Th2 or TC2 cells. These findings suggest that the prerequisites for Th2 and TC2 cell development are different in vivo than in vitro and may also explain why Th2 cells are more readily detected after immunisations or infections than TC2 cells in vivo.
Wohlleben
Gisela
G
Center for Infectious Diseases, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
Erb
Klaus J
KJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma