RESUMO
Chemokine receptor transcripts were defined among CD4+ T cells in lymph nodes of mice with type-1 and type-2 inflammation, respectively, elicited by mycobacterial and schistosomal Ag. CXCR3 and CCR6 transcripts were biased to type-1, and CCR4 transcripts increased in type-1 and type-2 populations. CCR3 and CCR5 signals were too weak to establish differences. CCR8 transcripts were not increased among unstimulated populations. Compared to naïve, type-1 and type-2 populations had reduced CCR7 and enhanced CXCR5 transcripts, consistent with a shift to memory cells. Subset depletion revealed that transcript expression was induced among CD44+ memory T cells. Surprisingly, CCR3 transcripts were enriched among CD44lo fractions. Ag stimulation augmented CXCR3, CCR4, and CCR8 but down-regulated CCR6 and CXCR5. CCR4 showed association with IFN-gamma- and IL-4-producing cells, but other receptor transcripts were expressed among IFN-gamma/IL-4 negative memory T cells. These studies provide several novel findings regarding Th cell chemokine receptor expression in vivo.
Assuntos
Antígenos de Bactérias/imunologia , Antígenos de Protozoários/imunologia , Regulação da Expressão Gênica , Mycobacterium tuberculosis/imunologia , Receptores de Quimiocinas/biossíntese , Schistosoma mansoni/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo , Tuberculina/imunologia , Animais , Feminino , Memória Imunológica , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-4/biossíntese , Interleucina-4/genética , Camundongos , Camundongos Endogâmicos CBA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores CCR3 , Receptores CCR4 , Receptores CCR6 , Receptores CCR7 , Receptores CCR8 , Receptores CXCR3 , Receptores CXCR5 , Receptores de Quimiocinas/genética , Receptores de Citocinas/biossíntese , Receptores de Citocinas/genética , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Monocyte chemotactic protein-3 (MCP-3/CCL7) has potent eosinophil chemoattractant properties. The present study determined its relative contribution to the formation of Th2 cytokine-mediated (type-2) eosinophil-rich interstitial lung granulomas induced by antigens of Schistosoma mansoni eggs. Both MCP-3 transcripts and protein levels were more strongly expressed in lungs with type-2 than with type-1 (mycobacterial antigen-elicited Th1-mediated) granulomas. In vivo treatment with neutralizing antibodies demonstrated that MCP-3 abrogated eosinophil accumulation in type-2 lesions by 40 to 50%. Immunohistochemical staining revealed that MCP-3 localized to vessels in or near granulomas suggesting that endothelial cells were an important in situ source of MCP-3. Maximal MCP-3 transcript expression was abrogated by anti-interleukin-4 treatment. Furthermore, cultured mouse lung endothelial cells displayed augmented MCP-3 production in response to interleukin-4. Together, these results suggest that MCP-3 contributes to a significant component of eosinophil recruitment in the type-2 interstitial granuloma formation and Th2 cytokines promote its production.
