TY - JOUR
T1 - Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from αβ TCR transgenic mice
T2 - IL-12 substitution for macrophages to stimulate IFN-γ production is IFN-γ-dependent
AU - Macatonia, Steven E.
AU - Hsleh, Chyi song
AU - Murphy, Kenneth M.
AU - O'garra, Anne
N1 - Funding Information:
We thank Dr Jim Cupp, Dixie Polakoff, and Eleni Callas for expert assistance with flow cytometry. We thank Lewis Lanier, Mark Doherty, Bob Coffman, Fiona Powrie, and Robin Slattery for useful discussion. We thank Jeanine Mattson and Janice Culpepper for providing us with IL-12. DNAX is supported by Schering Plough, NJ.
PY - 1993/9
Y1 - 1993/9
N2 - 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.
AB - 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.
KW - Dendritic cells
KW - IFN-γ
KW - IL-12
KW - Macrophages
KW - TCR transgenic T cells
UR - http://www.scopus.com/inward/record.url?scp=0027422313&partnerID=8YFLogxK
U2 - 10.1093/intimm/5.9.1119
DO - 10.1093/intimm/5.9.1119
M3 - Article
C2 - 7902129
AN - SCOPUS:0027422313
SN - 0953-8178
VL - 5
SP - 1119
EP - 1128
JO - International Immunology
JF - International Immunology
IS - 9
ER -