Adenoviral-mediated overexpression of monocyte chemoattractant protein-1 differentially alters the development of Th1 and Th2 type responses in vivo.
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-gamma 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.
Matsukawa
A
A
Department of Pathology, Division of Pulmonary Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Lukacs
N W
NW
Standiford
T J
TJ
Chensue
S W
SW
Kunkel
S L
SL
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000382:microbiology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014373:Tuberculin / Q000276:immunology
D018932:Chemokine CCL2; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D014373:Tuberculin