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0014-2980/00/0909-2669$17.50+.50/0 WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000 Alternatively activated macrophages induced
 

Summary: 0014-2980/00/0909-2669$17.50+.50/0 WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
Alternatively activated macrophages induced
by nematode infection inhibit proliferation
via cell-to-cell contact
P'ng Loke, Andrew S. MacDonald, Amy Robb, Rick M. Maizels and Judith E. Allen
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, GB
The cytokine microenvironment is thought to play an important role in the generation of
immunoregulatory cells. Nematode infections are commonly associated with Th2 cytokines
and hyporesponsive T cells. Here we show that IL-4-dependent macrophages recruited in
vivo by the nematode parasite Brugia malayi actively suppress the proliferation of lympho-
cytes on co-culture in vitro. These alternatively activated macrophages block proliferation by
cell-to-cell contact, implicating a receptor-mediated mechanism. Further, the proliferative
block is reversible and is not a result of apoptosis. Suppressed cells accumulate in the G1
and G2/M phase of the cell cycle. Interestingly, the G1 and G2/M block correlates with
increased levels of Ki-67 protein, suggesting a mechanism that affects degradation of cell
cycle proteins. We also show that, in addition to lymphocyte cell lines of murine origin, these
suppressive cells can inhibit proliferation of a wide range of transformed human carcinoma
lines. Our data reveal a novel mechanism of proliferative suppression induced by a parasitic
nematode that acts via IL-4-dependent macrophages. These macrophages may function as
important immune regulatory cells in both infectious and noninfectious disease contexts.

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh
Maizels, Rick - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine; Environmental Sciences and Ecology