M. Desmedt et al., MACROPHAGES INDUCE CELLULAR-IMMUNITY BY ACTIVATING TH1 CELL RESPONSESAND SUPPRESSING TH2 CELL RESPONSES, The Journal of immunology, 160(11), 1998, pp. 5300-5308
Differentiation of naive CD4(+) T cells (Th0) into Th1 or Th2 cells de
termines whether antigen will raise a cellular or a humoral immune res
ponse, The maturation pathway chosen by the Th0 cell is often decisive
for the outcome of disease and depends among others on the (co-)stimu
latory attributes of the APC and the nature and abundance of cytokines
provided by the APC and the microenvironment. In this study, we used
macrophages, loaded ex vivo with antigen, for inciting Th0 activation
and differentiation in vivo. The macrophages were derived from a clona
l, immortalized population that both functionally and phenotypically e
xpressed features characteristic of mature macrophages. Injection into
syngeneic mice of IFN-gamma-treated, Ag-loaded macrophages induced a
primary T cell response, indicated by the occurrence of a proliferativ
e response in vitro after restimulation of splenocytes with Ag. analys
is of the accompanying cytokine secretion revealed high numbers of IFN
-gamma-producing Th1 cells and only a few IL-4-secreting Th2 cells. Th
is dominance of Th1 cells had functional implications, reflected in th
e high titer of Th1 cell-dependent IgG2 Abs and the absence of IgG1, c
haracteristic of humoral immunity. Moreover, administration of Ag-load
ed macrophages to mice with an ongoing Th1/Th2 response resulted in a
complete suppression of IgG1 production, whereas IgG2 levels remained
unaffected, These results demonstrate that macrophages exert APC activ
ity in the organism, strongly skew primary responses to cellular immun
ity, and in addition suppress an already generated Th2-dependent humor
al response, thus characterizing these cells as Th1-oriented APC.