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F4/80 Alternatively Activated Macrophages Control CD4 T Cell Hyporesponsiveness at Sites Peripheral to Filarial
 

Summary: F4/80 Alternatively Activated Macrophages Control CD4 T
Cell Hyporesponsiveness at Sites Peripheral to Filarial
Infection1
Matthew D. Taylor, Anjanette Harris, Meera G. Nair, Rick M. Maizels,2
and Judith E. Allen2
Both T cells and APC have been strongly implicated in the immune suppression observed during filarial nematode infections, but
their relative roles are poorly understood, particularly in regard to timing and locality of action. Using Litomosoides sigmodontis
infection of susceptible BALB/c mice, we have studied the progression of filarial immunosuppression leading to patent infection
with blood microfilaremia. Patent infection is associated with decreased immune responsiveness in the draining thoracic lymph
nodes (tLN) and intrinsically hyporesponsive CD4 T cells at the infection site. We now show that we are able to separate, both
in time and space, different suppressive mechanisms and cell populations that contribute to filarial hyporesponsiveness. L. sig-
modontis infection recruited a F4/80 population of alternatively activated macrophages that potently inhibited Ag-specific CD4
T cell proliferative responses even in the presence of competent naive APC. T cell responsiveness was partially restored by
neutralizing TGF- , but not by blocking IL-10 or CTLA-4 signaling. During prepatent infection, the macrophage population was
restricted to the infection site. However, once infection became patent with systemic release of microfilariae, the suppressive
macrophage activity extended peripherally into the tLN. In contrast, the hyporesponsive CD4 T cell phenotype remained
localized at the infection site, and the tLN CD4 T cell population recovered full Ag responsiveness in the absence of suppressive
macrophages. Filarial immunosuppression, therefore, evolves over time at sites increasingly distal to infection, and the mecha-
nisms of filarial down-regulation are dependent on proximity to the infection site. The Journal of Immunology, 2006, 176:
69186927.

  

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