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Departments of Pathology and
*
Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and
Department of Pathology, Veterans Administration, Ann Arbor, MI 48109
The expression of chemokines during an immune response may
participate in determining the intensity and type of the developing
immune response. In the present study, we have examined the effect of
overexpressing monocyte chemoattractant protein (MCP)-1 at the site of
immunization during different stages of Th1- and Th2-type granulomatous
responses. The overexpression of MCP-1 by MCP-1 adenovirus during the
sensitization phase of the purified protein derivative Th1-type model
significantly reduced the elicitation of the granulomatous response. In
contrast, the overexpression of MCP-1 during the sensitization phase of
the schistosome egg Ag Th2 response led to an enhanced granulomatous
reaction. When cytokines were examined upon restimulation of
splenocytes ex vivo, an altered cytokine profile was observed, as
compared with control mice. IFN-
and IL-12 were significantly
reduced in the purified protein derivative Th1-type response, whereas
IL-10 and IL-13 were up-regulated in the schistosome egg Ag Th2-type
response. The regulation of the immune response was further examined by
using the MCP-1 adenovirus at later time points during the elicitation
phase. When MCP-1 was overexpressed during the elicitation phase of the
responses, neither the Th1-type nor the Th2-type granuloma was altered.
Likewise, the cytokine profiles after restimulation of splenocytes ex
vivo were unchanged. Thus, the function of MCP-1 may depend on the
stage and type of immune response.
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