Accumulation of effector CD4 T cells during type 2 immune responses is negatively regulated by Stat6.
Th2 cells are important effector cells during allergic disorders and parasite infections. Efficient differentiation of Th2 cells requires signaling via the IL-4R and the transcription factor Stat6. Stat6 is further implicated in Th2 cell recruitment to the lung and might be required for the survival of memory Th2 cells. We analyzed the role of Stat6 in T cell expansion, survival, and recruitment to the lung using competitive adoptive transfer experiments and infection with the helminth parasite Nippostrongylus brasiliensis. Stat6 was not required in T cells or other cell types for recruitment of in vivo-generated Th2 cells to the lung. Functional analysis of Th2 memory cells revealed that Stat6 signaling in CD4 T cells was dispensable for memory cell generation, expansion, and cytokine secretion. However, Stat6-deficient T cells survived better than wild-type T cells, resulting in higher accumulation in the bronchoalveolar lavage, lung, and lymph nodes. This demonstrates that effector T cell expansion is negatively controlled by a novel Stat6-dependent mechanism which probably serves to limit the number of effector T cells during the acute phase of the immune response and thereby lowers the risk of bystander toxicity against healthy tissues.
King
Susan B S
SB
Institute for Immunology, University of Munich, Munich, Germany.
Knorn
Anna M
AM
Ohnmacht
Caspar
C
Voehringer
David
D
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009559:Nippostrongylus; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse