RESUMO
Th2 cells are recruited to the lung where they mediate the asthma phenotype. Since the molecular mechanisms regulating Th2 cell trafficking remain unknown, we sought to determine whether trafficking of Th2 cells into the lung is mediated by G alpha i-coupled chemoattractant receptors. We show here that in contrast to untreated Th2 cells, pertussis toxin-treated Th2 cells were unable to traffic into the lung, airways, or lymph nodes following Ag challenge and therefore were unable to induce allergic inflammation in vivo. Pertussis toxin-treated Th2 cells were functional cells, however, and when directly instilled into the airways of mice, bypassing their need to traffic to the lung, were able to induce airway eosinophilic inflammation. These studies conclusively demonstrate that trafficking of Th2 cells into the lung is an active process dependent on chemoattractant receptors.
Assuntos
Movimento Celular/imunologia , Receptores de Quimiocinas/fisiologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Transferência Adotiva , Aerossóis , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Inibição de Migração Celular , Células Cultivadas , Quimiotaxia de Leucócito/imunologia , Citocinas/metabolismo , Epitopos de Linfócito T/administração & dosagem , Epitopos de Linfócito T/imunologia , Inflamação/imunologia , Inflamação/patologia , Integrinas/biossíntese , Intubação Intratraqueal , Linfonodos/citologia , Linfonodos/imunologia , Linfonodos/patologia , Ativação Linfocitária/imunologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Muco/metabolismo , Nebulizadores e Vaporizadores , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Toxina Pertussis , Eosinofilia Pulmonar/imunologia , Eosinofilia Pulmonar/patologia , Hipersensibilidade Respiratória/patologia , Células Th2/patologia , Células Th2/transplante , Fatores de Virulência de Bordetella/administração & dosagem , Fatores de Virulência de Bordetella/imunologia , Fatores de Virulência de Bordetella/farmacologiaRESUMO
Leukotriene B4 (LTB4) was originally described as a potent lipid myeloid cell chemoattractant, rapidly generated from innate immune cells, that activates leukocytes through the G protein-coupled receptor BLT1. We report here that BLT1 is expressed on effector CD4+ T cells generated in vitro as well as in vivo when effector T cells migrate out of the lymphoid compartment and are recruited into peripheral tissues. BLT1 mediated LTB4-induced T helper type 1 (T(H)1) and T(H)2 cell chemotaxis and firm adhesion to endothelial cells under flow, as well as early CD4+ and CD8+ T cell recruitment into the airway in an asthma model. Our findings show that the LTB4-BLT1 pathway is involved in linking early immune system activation and early effector T cell recruitment.