BALB/c mice bearing a transgenic IL-12 receptor beta 2 gene exhibit a nonhealing phenotype to Leishmania major infection despite intact IL-12 signaling.
J Immunol
; 166(11): 6776-83, 2001 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-11359836
ABSTRACT
In BALB/c mice infected with Leishmania major, early secretion of IL-4 leads to a Th2-type response and nonhealing. We explored the role of IL-4-induced down-regulation of the IL-12Rbeta2 chain in the establishment of this Th2 response. First, we showed that the draining lymph nodes of resistant C57BL/6 mice infected with L. major were enriched in CD4+/IL-12Rbeta2 chain+ cells producing IFN-gamma. Next, we demonstrated that BALB/c background mice bearing an IL-12Rbeta2-chain transgene manifested a nonhealing phenotype similar to wild-type littermates despite the persistence of their ability to undergo STAT4 activation. Finally, we found that such transgenic mice display more severe infection than wild-type littermates when treated with IL-12 7 days after infection, and under this condition, the mice display increased Leishmania Ag-induced IL-4 secretion. These studies indicate that although CD4+/IL-12Rbeta2 chain+ T cells are important components of the Th1 response, maintenance of IL-12Rbeta2 chain expression is not sufficient to change a Th2 response to a Th1 response in vivo and thus to allow BALB/c mice to heal L. major infection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
3_ND
Problema de saúde:
3_zoonosis
Assunto principal:
Camundongos Transgênicos
/
Leishmaniose Cutânea
/
Receptores de Interleucina
/
Leishmania major
/
Interleucina-12
/
Transgenes
/
Camundongos Endogâmicos BALB C
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos