Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from alpha beta TCR transgenic mice: IL-12 substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent.
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 alpha beta TCR transgenic mice. Purified dendritic cells were the principal cell required for induction of primary ovalbumin 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-gamma 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-gamma was dependent on IFN-gamma.
Macatonia
S E
SE
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
Hsieh
C S
CS
Murphy
K M
KM
O'Garra
A
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018664:Interleukin-12; D007371:Interferon-gamma