IFN-γ mediates the death of Th1 cells in a paracrine manner

Kathryn E. Foulds, Masashi J. Rotte, Michael A. Paley, Babu Singh, Daniel C. Douek, Brenna J. Hill, John J. O'Shea, Wendy T. Watford, Robert A. Seder, Chang You Wu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Th1 cells have different capacities to develop into memory cells based on their production of IFN-γ. In this study, the mechanism by which a homogenous population of IFN-γ-producing CD4 T cells was eliminated in vivo was assessed. When such cells were transferred into naive mice and activated with Ag, a striking decrease in the frequency of cells in the spleen and lung was observed. However, administration of neutralizing anti-IFN-γ Ab at the time of Ag challenge largely prevented the elimination of such cells. To determine whether IFN-γ was mediating its effects directly and/or indirectly, the ability of IFN-γ to effectively signal in such cells was assessed in vitro. Indeed, there was reduced phosphorylation of STAT1 in response to IFN-γ as well as markedly reduced expression of the IFN-γR β-chain. Furthermore, transfer of such cells into IFN-γR-deficient mice limited their death following activation with Ag. Together, these data suggest that IFN-γ acts in a paracrine manner to mediate the death of activated IFN-γ-producing Th1 cells. In contrast to Ag stimulation, administration of CpG alone resulted in the elimination of Th1 cells in IFN-γR-/- mice. These results show that in response to Ag stimulation, the death of IFN-γ-producing effector Th1 cells is controlled in an IFN-γ-dependent manner, whereas in response to innate activation, the death of IFN-γ-producing Th1 cells can occur through an IFN-γ-independent pathway. Collectively, these data show the multiple mechanisms by which Th1 effector cells are efficiently eliminated in vivo.

Original languageEnglish
Pages (from-to)842-849
Number of pages8
JournalJournal of Immunology
Volume180
Issue number2
DOIs
StatePublished - Jan 15 2008

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