Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from αβ TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-γ production is IFN-γ-dependent

Steven E. Macatonia, Chyi song Hsleh, Kenneth M. Murphy, Anne O'garra

Research output: Contribution to journalArticle

324 Scopus citations

Abstract

We have examined the antigen presenting cell (APC) requirements for primary T cell activation and T helper (Th) cell phenotype differentiation using naive CD4+ T cells from αβ TCR transgenic mice. Purified dendritic cells were the principal cell required for induction of primary ovalbumln peptide specific T cell activation and clonal expansion. However, dendritic cells did not induce differentiation of T cells toward Th1 or Th2 phenotype. Addition of IL-4 during primary dendritic cell stimulations of T cells resulted in the development of a Th2 phenotype which produced high levels of IL-4 during secondary and tertiary stimulation. In contrast, development of Th1 cells producing high levels of IFN-γ could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages. Addition of splenic or peritoneal B cells did not induce Th1 development. Activated splenic macrophages induced Th1 development via a non-MHC restricted mechanism. Thus, requirements for induction of proliferation of naive CD4+ T cells are distinct from those directing Th1 phenotype development. IL-12 could replace the requirement for macrophages to induce Th1 development when T cells were activated with dendritic cells. Furthermore, this IL-12 mediated development of Th1 cells producing high levels of IFN-γ was dependent on IFN-γ.

Original languageEnglish
Pages (from-to)1119-1128
Number of pages10
JournalInternational Immunology
Volume5
Issue number9
DOIs
StatePublished - Sep 1 1993

Keywords

  • Dendritic cells
  • IFN-γ
  • IL-12
  • Macrophages
  • TCR transgenic T cells

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